Approximately 8.5%–16.2% of childhood cancers are associated with a pathogenic/likely pathogenic germline variant—a prevalence that is likely to rise with improvements in phenotype recognition, sequencing, and variant validation. One highly informative, classical hereditary cancer predisposition syndrome is Li–Fraumeni syndrome (LFS), associated with germline variants in the TP53 tumor suppressor gene, and a >90% cumulative lifetime cancer risk. In seeking to improve outcomes for young LFS patients, we must improve the specificity and sensitivity of existing cancer surveillance programs and explore how to complement early detection strategies with pharmacology-based risk-reduction interventions. Here, we describe novel precision screening technologies and clinical strategies for cancer risk reduction. In particular, we summarize the biomarkers for early diagnosis and risk stratification of LFS patients from birth, noninvasive and machine learning–based cancer screening, and drugs that have shown the potential to be repurposed for cancer prevention.

Most childhood cancers possess distinct clinicopathological profiles from those seen in adulthood, reflecting their divergent mechanisms of carcinogenesis. Rather than depending on the decades-long, stepwise accumulation of changes within a mature cell that defines adult carcinomas, many pediatric malignancies emerge rapidly as the consequence of random errors during development. These errors—whether they be genetic, epigenetic, or microenvironmental—characteristically block maturation, resulting in phenotypically primitive neoplasms. Only an event that falls within a narrow set of spatiotemporal parameters will forge a malignant clone; if it occurs too soon then the event might be lethal, or negatively selected against, while if it is too late or in an incorrectly primed precursor cell then the necessary intracellular conditions for transformation will not be met. The precise characterization of these changes, through the study of normal tissues and tumors from patients and model systems, will be essential if we are to develop new strategies to diagnose, treat, and perhaps even prevent childhood cancer.

Redox reactions control fundamental biochemical processes, including energy production, metabolism, respiration, detoxification, and signal transduction. Cancer cells, due to their generally active metabolism for sustained proliferation, produce high levels of reactive oxygen species (ROS) compared to normal cells and are equipped with antioxidant defense systems to counteract the detrimental effects of ROS to maintain redox homeostasis. The KEAP1-NRF2 system plays a major role in sensing and regulating endogenous antioxidant defenses in both normal and cancer cells, creating a bivalent contribution of NRF2 to cancer prevention and therapy. Cancer cells hijack the NRF2-dependent antioxidant program and exploit a very unique metabolism as a trade-off for enhanced antioxidant capacity. This work provides an overview of redox metabolism in cancer cells, highlighting the role of the KEAP1-NRF2 system, selenoproteins, sulfur metabolism, heme/iron metabolism, and antioxidants. Finally, we describe therapeutic approaches that can be leveraged to target redox metabolism in cancer.

The broad application of noninvasive imaging has transformed preclinical cancer research, providing a powerful means to measure dynamic processes in living animals. While imaging technologies are routinely used to monitor tumor growth in model systems, their greatest potential lies in their ability to answer fundamental biological questions. Here we present the broad range of potential imaging applications according to the needs of a cancer biologist with a focus on some of the common biological processes that can be used to visualize and measure. Topics include imaging metastasis; biophysical properties such as perfusion, diffusion, oxygenation, and stiffness; imaging the immune system and tumor microenvironment; and imaging tumor metabolism. We also discuss the general ability of each approach and the level of training needed to both acquire and analyze images. The overall goal is to provide a practical guide for cancer biologists interested in answering biological questions with preclinical imaging technologies.

Vision is initiated by capturing photons in highly specialized sensory cilia known as the photoreceptor outer segment. Because of its lipid and protein composition, the outer segments are prone to photo-oxidation, requiring photoreceptors to have robust antioxidant defenses and high metabolic synthesis rates to regenerate the outer segments every 10 days. Both processes required high levels of glucose uptake and utilization. Retinitis pigmentosa is a prevalent form of inherited retinal degeneration characterized by initial loss of low-light vision caused by the death of rod photoreceptors. In this disease, rods die as a direct effect of an inherited mutation. Following the loss of rods, cones eventually degenerate, resulting in complete blindness. The progression of vision loss in retinitis pigmentosa suggested that rod photoreceptors were necessary to maintain healthy cones. We identified a protein secreted by rods that functions to promote cone survival, and we named it rod-derived cone viability factor (RdCVF). RdCVF is encoded by an alternative splice product of the nucleoredoxin-like 1 (NXNL1) gene, and RdCVF was found to accelerate the uptake of glucose by cones. Without RdCVF, cones eventually die because of compromised glucose uptake and utilization. The NXNL1 gene also encodes for the thioredoxin RdCVFL, which reduces cysteines in photoreceptor proteins that are oxidized, providing a defense against radical oxygen species. We will review here the main steps of discovering this novel intercellular signaling currently under translation as a broad-spectrum treatment for retinitis pigmentosa.

Background

In an evolving landscape of practices and policies, reviewing and incorporating the latest scientific evidence is necessary to ensure optimal clinical management for people with opioid use disorder. We provide a synopsis of the 2024 update of the 2018 National Guideline for the Clinical Management of Opioid Use Disorder, from the Canadian Research Initiative in Substance Matters.

The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the third Respiratory Failure and Mechanical Ventilation Conference in February 2024. The conference covered key points of acute and chronic respiratory failure in adults. During the 3-day conference ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. In this article, lectures delivered during the event have been summarised by early career members of the Assembly and take-home messages highlighted.

Stage III nonsmall cell lung cancer (NSCLC) represents a wide range of tumour (T1 to T4) and nodal (N0 to N3) components, requiring variable management and a multidisciplinary approach. Recent advancements in minimally invasive techniques, molecular biology and novel drug discoveries have accelerated the refinement of stage III NSCLC management. The latest developments in staging include the forthcoming update of the nodal component in the 9th TNM (tumour–node–metastasis) edition, which emphasises the critical role for endobronchial ultrasonography in mediastinal staging. Recent treatment developments include the use of immunotherapy and targeted molecular therapy in both the neoadjuvant and adjuvant setting, either in combination with other modalities or used alone as consolidation. Surgical and radiotherapy advancements have further enhanced patient outcomes. These developments have significantly improved the prognosis for patients with stage III NSCLC. Fast-changing recommendations have also brought about a challenge, with clinicians facing a number of options to choose from. Therefore, a multimodal approach by a multidisciplinary team has become even more crucial in managing stage III NSCLC.

Advancements in immunotherapy in the perioperative setting have revolutionised the treatment of resectable nonsmall cell lung cancer (NSCLC). Here we present the methodology and results of the clinical trial CheckMate 816 demonstrating the benefit of neoadjuvant therapy with nivolumab plus chemotherapy compared with chemotherapy alone. Furthermore, this article discusses the implications for future practice in resectable NSCLC and the need for future research.

Bone marrow transplantation, now often known as haematopoietic stem cell transplantation (HSCT), is a complex choreographed procedure used to treat both acquired and inherited disorders of the bone marrow. It has proven invaluable as therapy for haematological and immunological disorders, and more recently in the treatment of metabolic and enzyme disorders. As the number of performed transplants grows annually, and with patients enjoying improved survival, a knowledge of both early and late complications of HSCT is essential for respiratory trainees and physicians in practice. This article highlights the spectrum of respiratory complications, both infectious and non-infectious, the timeline of their likely occurrence, and the approaches used for diagnosis and treatment, keeping in mind that more than one entity may occur simultaneously. As respiratory issues are often a leading cause of short- and long-term morbidity, consideration of a combined haematology/respiratory clinic may prove useful in this patient population.

Lung cancer is one of the leading causes of death worldwide. It can broadly be divided into small cell lung cancer (SCLC) and nonsmall cell lung cancer. There have been many advances over the recent years in both fields. The purpose of this review is to provide a concise summary of SCLC for the general respiratory readership.

Central sleep apnoea (CSA) is characterised by recurrent episodes of airway cessation or reduction in the absence of respiratory effort. Although CSA is less common than obstructive sleep apnoea, it shares similar symptoms. CSA can be secondary to various medical conditions, high altitude and medication exposure. CSA can also emerge during obstructive sleep apnoea therapy. There are a range of treatment options and selecting the right therapy requires an understanding of the pathophysiology of CSA. This review explores the aetiology, pathophysiology and clinical management of non-hypercapnic CSA.

Chronic pulmonary aspergillosis has a range of manifestations from indolent nodules to semi-invasive infection. Patients may be asymptomatic or have chronic symptoms such as cough and weight loss or present with life-threatening haemoptysis. The physician can choose from a range of available therapies including medical therapy with antifungals, minimally invasive therapy with intracavitary antifungal therapy and surgery involving open thoracotomy or video-assisted thoracoscopic surgery. The patients with the most severe forms of pulmonary infection may not be surgical candidates due to their underlying pulmonary condition. The management of haemoptysis can include tranexamic acid, bronchial artery embolisation, antifungals or surgery. There are few controlled studies to inform clinicians managing complex cases, so a multidisciplinary approach may be helpful.

For many severe lung diseases, non-invasive biomarkers from imaging could improve early detection of lung injury or disease onset, establish a diagnosis, or help follow-up disease progression and treatment strategies. Imaging of the thorax and lung is challenging due to its size, respiration movement, transferred cardiac pulsation, vast density range and gravitation sensitivity. However, there is extensive ongoing research in this fast-evolving field. Recent improvements in spatial imaging have allowed us to study the three-dimensional structure of the lung, providing both spatial architecture and transcriptomic information at single-cell resolution. This fast progression, however, comes with several challenges, including significant image file storage and network capacity issues, increased costs, data processing and analysis, the role of artificial intelligence and machine learning, and mechanisms to combine several modalities. In this review, we provide an overview of advances and current issues in the field of spatial lung imaging.

Palliative care pertains to the holistic multidimensional concept of "patient-centred" care. It is an interprofessional specialty, primarily aiming to improve quality of care for cancer patients and their families, from the time of diagnosis of malignant disease, over the continuum of cancer care, and extending after the patient's death to the period of bereavement to support the patient's family. There are various complex and frequently unmet needs of lung cancer patients and their families/caregivers, not only physical but also psychological, social, spiritual and cultural. Systematic monitoring of patients’ symptoms using validated questionnaires and patient-reported outcomes (PROs), on a regular basis, is highly encouraged and recommended in recent guidelines on the role of PRO measures in the continuum of cancer clinical care. It improves patient–physician communication, physician awareness of symptoms, symptom control, patient satisfaction, health-related quality of life and cost-effectiveness. This implies that all treating physicians should improve their skills in communication with lung cancer patients/relatives and become more familiar with this multidimensional assessment, repeatedly screening patients for palliative care needs. Therefore, they should receive education and training to develop palliative care knowledge, skills and attitudes. This review is dedicated to lung cancer palliative care essentials that should be within the competences of treating physicians, i.e. pneumologists/thoracic oncologists.

Imaging methods are fundamental tools to detect and diagnose lung diseases, monitor their treatment and detect possible complications. Each modality, starting from classical chest radiographs and computed tomography, as well as the ever more popular and easily available thoracic ultrasound, magnetic resonance imaging and nuclear medicine methods, and new techniques such as photon counting computed tomography, radiomics and application of artificial intelligence, has its strong and weak points, which we should be familiar with to properly choose between the methods and interpret their results. In this review, we present the indications, strengths and main limitations of methods for chest imaging.

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Jade Ho explains what is possible for university students when they are given opportunities to learn about –and get involved with– social justice and labour issues in their own communities.

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A new report by the global union Education International shows that AI can degrade the quality of education, worsen working conditions for teachers and provide inferior schooling for students.

The post Artificial Intelligence can cause fake education appeared first on rabble.ca.

So far, the Israeli leadership seems unmoved by U.S. President Biden’s quiet suggestions for a pause in hostilities in Gaza.

The post Saving Palestinian lives will save Israeli lives appeared first on rabble.ca.

The current growth and consumption based economy is not sustainable. The world must move towards a circular economy and sustainability.

The post Degrowth, green energy, social equity, and circular economy appeared first on rabble.ca.

With 420,000 Quebec public sector workers on strike on Monday, and with little progress in negotiations, the Front Commun promises further strike action.

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The City of Vancouver council has reneged on a previous commitment to a living wage for its employees.

The post City of Vancouver to lowest paid workers: Let them eat cuts! appeared first on rabble.ca.

Deepfakes can be close to indistinguishable from authentic video, and are now being used to perpetrate gender based abuse.

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Danielle Smith says she is “100 per cent committed” to a leaked plan to replace Alberta Health Services with new health boards, agencies, bureaucracy, all directed out of her office.

The post UCP set to announce plan to bust up AHS appeared first on rabble.ca.

In August, fellow reporter Jason Patinkin and I crossed on foot from northern Uganda into rebel-held South Sudan. Over the course of four days, we walked more than 40 miles through the bush, escorted by rebel soldiers, to shed light on one of the world’s most underreported conflicts.

Reporting on South Sudan’s war, which began in 2013, has always been a challenge due to the risk and logistical hurdles associated with accessing remote areas where fighting takes place. But over the past year, covering the war and its humanitarian fallout has become particularly difficult. Since the beginning of this year, South Sudan’s government has banned at least 20 foreign journalists in an apparent effort to silence reporters who had a track record of critically reporting on the government.

This systematic crackdown on the foreign press (South Sudanese journalists have long risked imprisonment and death for doing their work) coincided with two important developments. In November 2016, the United Nations warned that the violence being committed against civilians in the southern region of Equatoria risked spiraling into genocide. Then, in February, the UN declared a man-made famine, warning that 100,000 people were at risk of starving to death as a result of civil war.

Journalists seeking to cover these events were left with two equally unsavory options: self-censorship or a risky trip to rebel-held parts of the country. Only a handful of journalists have attempted the latter since fighting escalated in July last year. For us, this was our second embed with the rebels this year.

We set off from a town in northern Uganda at five in the morning, bouncing along a bumpy dirt track towards the South Sudan border. Crammed into our four-wheel drive were rebel commander Martin Abucha, a dual American and South Sudanese citizen who we planned to profile for our PBS NewsHour Weekend segment, a couple of guides, and several duffle bags stuffed with our tents, sleeping bags, emergency medical kits and provisions to last us four days.

Just as the sun began to rise above a distant range of hills that we aimed to cross later that day, our car came to a halt in front of a stream. Because of the rainy reason, it carried more water than usual. It was time to disembark and start walking, or “footing,” as South Sudanese tend to call it.

We took off our shoes and waded through the stream’s chilly waters. This was the first of a many rivers we’d have to cross along the way, either on foot or in small flimsy canoes dug out from tree trunks. Each time, we dreaded the idea of falling in with our camera gear.

The first part of our journey in northern Uganda felt very much like a hike through a national park. Passing beautiful landscapes and idyllic farming villages, one could almost forget we were headed into a war zone — but we were about to get a reality check.

We had just crossed into South Sudan when out of nowhere, two dozen armed men popped out of the tall grass and surrounded us at gunpoint.

“Stop! Who are you and where are you going?” a soldier called out in Juba Arabic from his hideout no more than 20 yards away, pointing his AK47 at us. Another one next to him had a rocket-propelled grenade propped on his shoulder, also unequivocally aiming it in our direction.

Instinctively, we threw our hands in the air and exchanged a baffled glance. Had we accidentally bumped into government soldiers? Or perhaps we had come onto the “wrong” rebels? Abucha’s group, called the Sudan People’s Liberation Army In Opposition, is the biggest but not the only armed group in Equatoria, an area rife with rival militia and bandits who exploit the security vacuum left by war.

To our relief, and only after Abucha answered a series of questions, this routine security check quickly gave way to a warm welcome. The platoon would be our escort for the next four days as we trekked to their base and to Loa, Abucha’s hometown.

Keeping up with the rebels was no easy task. Given the country’s pervasive lack of basic infrastructure, South Sudanese grow up walking for dozens of miles just to go about their daily lives. For sedentary Westerners, keeping the target pace of “two meters per second” (around five miles an hour) proved challenging amid 90-degree temperatures, all while filming and plowing our way through dense, itchy elephant grass.

The upside of the cumbersome terrain was that it kept us safe. During our four-day trip, we didn’t cross a single road, instead walking along a dizzying network of narrow bush paths the rebels seemed to know like the backs of their hands. An unwanted encounter with government troops, who tended to stick to roads and move around in vehicles as opposed to on foot, was highly unlikely.

The closest we got to government-controlled area was a visit to Loa, located just two kilometers away from a main road frequently patrolled by government soldiers. We couldn’t stay long, but the hour we spent on the ground offered us a glimpse into what villages must look like in many parts of Equatoria: burned mud huts, looted schools and clinics, fallow fields and – most strikingly – no civilians.

The war has had a devastating impact on South Sudanese communities like the one in Loa, but much of it has remained out of the limelight of international media. Our four-day venture into rebel-held South Sudan offered us a rare opportunity to report ground truths, and we are thankful for that.

The post Column: Why reporting from South Sudan is so difficult — and critically needed appeared first on PBS NewsHour.

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The United Nations says South Sudan’s four-year-old civil war has left half of the nation’s population — 6 million people — in need of humanitarian aid. The conflict began when South Sudan’s army split between factions loyal to President Salva Kiir and former Vice President Riek Machar. The two men mobilized their respective tribes, the Dinka and the Nuer. The war has caused what is now one of the world’s worst refugee crises.

SIMONA FOLTYN: Civil war is emptying huge swaths of South Sudan. The violence has uprooted four million people, including two million who’ve fled to neighboring countries. In the last year, more than a million South Sudanese have poured into northern Uganda alone, crossing makeshift bridges like this one to flee fighting, hunger, and brutal attacks on civilians.

SEME LUPAI, REFUGEE: They started fighting very, very severely. So that made us to escape with our properties to this side.

SIMONA FOLTYN: When Seme Lupai’s family went to one of the refugee camps, initially, he stayed behind to look after the family’s most precious commodity — their cattle. He hid for a year to escape the violence. The refugees carry whatever they can salvage — mattresses, pots, clothes, notebooks — remnants of once peaceful lives turned upside down. At checkpoints, Ugandan soldiers search their belongings for weapons, before the refugees proceed to reception centers. After entering Uganda, the refugees sign in at small waystations. For many, it’s the first night spent in safety after walking for days to escape fighting. Levi Arike fled with his wife and four children.

LEVI ARIKE, REFUGEE: When the gunshots started, we laid under a tree with the whole family, because there was nowhere else to hide. We waited for the fighting to stop, and then we got up and started walking to Uganda.

SIMONA FOLTYN: Uganda now shoulders most of the burden of Africa’s biggest refugee crisis, managing a constellation of camps which require food, water, healthcare, and policing. At Imvepi Camp, now home to more than 120,000 South Sudanese, new arrivals receive vaccinations, hot meals, and basic items such as soap and plastic tarps to build a house. The government also gives each refugee family a small plot of land, about a twentieth of an acre, where they can build a tent shelter and grow crops to eat or sell. But the land often proves too rocky for farming.

SIMONA FOLTYN, IMVEPI REFUGEE CAMP, NORTHERN UGANDA: After completing the registration process, the new arrivals will receive their plot, to start a new life as refugees in Uganda. While they are safe here, there are many challenges ahead, not least processing the trauma of what they experienced back home.

This woman, who we’ll call “Agnes,” agreed to tell us about her harrowing experience. She says four government soldiers from President Salva Kiir’s Dinka tribe stopped her as she was fleeing South Sudan and raped her right in front of her family.

AGNES (translated to English): When they started raping me, they told me not to raise alarm, otherwise they would shoot me. Still when I’m sleeping, I’m dreaming of the Dinka, that they are coming to rape me again.

SIMONA FOLTYN: How often do you have those dreams?

AGNES: Daily, every time I lie down, those dreams come.

SIMONA FOLTYN: A recent Human Rights Watch report on South Sudan found “…a clear pattern of government forces unlawfully targeting civilians for killings, rapes, torture…and destruction of property..” The victims are from ethnic groups suspected to support the rebels.

AGNES: They are doing it, because they know very well that those soldiers are our brothers. So they do it to punish them..

SIMONA FOLTYN: Although the rebels, known as the Sudan People’s Liberation Army In Opposition, purport to protect local communities, there are also reports of their fighters assaulting civilians near the Ugandan border. Josephine Yanya told us she didn’t feel safe in the presence of either side’s soldiers. Her family and neighbors fled their village after government soldiers killed her uncle.

They hid in the mountains only to find themselves under attack again, this time by opposition fighters from the Nuer tribe loyal to former vice president Riek Machar. Yanya says ethnic Nuer soldiers from the SPLA-IO rebel group raped a member of her group and stole her father’s’ cattle.

JOSEPHINE YANYA (translated to English): Before we were thinking that the rebels would protect us, but if they are lacking food, they just come and take things by force.

SIMONA FOLTYN: With nowhere left to hide, Yanya fled to Uganda with her son.
But instead of finding a place to rebuild their lives, they are in limbo. And aid groups don’t have enough food to distribute.

JOSEPHINE YANYA (translated to English):We are getting small food rations. I know it won’t be enough even for one month.

SIMONA FOLTYN: According to the United Nations, the international community has given less than a-third of the $1.4 billion dollars needed for the refugee response in South Sudan’s neighboring countries. These refugees foresee more hardship and have no idea when they might return home.

JOSEPHINE YANYA (translated to English): I’m always praying for peace in South Sudan, and until then, I’ll just stay here.

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