bluuebunny/crossref_metadata_2025 huggingface dataset:
NanoLAS: a comprehensive nanobody database with data integration, consolidation and application
Authors: Xiong Shuchang , Liu Zhengwen , Yi Xin , Liu Kai , Huang Bingding , Wang Xin
Published: February 2024

Nanobodies, a unique subclass of antibodies first discovered in camelid animals, are composed solely of a single heavy chain’s variable region. Their significantly reduced molecular weight, in comparison to conventional antibodies, confers numerous advantages in the treatment of various diseases. As research and applications involving nanobodies expand, the quantity of identified nanobodies is also rapidly growing. However, the existing antibody databases are deficient in type and coverage, failing to satisfy the comprehensive needs of researchers and thus impeding progress in nanobody research.

In response to this, we have amalgamated data from multiple sources to successfully assemble a new and comprehensive nanobody database. This database has currently included the latest nanobody data and provides researchers with an excellent search and data display interface, thus facilitating the progression of nanobody research and their application in disease treatment.

In summary, the newly constructed Nanobody Library and Archive System may significantly enhance the retrieval efficiency and application potential of nanobodies. We envision that Nanobody Library and Archive System will serve as an accessible, robust and efficient tool for nanobody research and development, propelling advancements in the field of biomedicine.

Database URL: https://www.nanolas.cloud
Dependent observations in clinical research
Authors: Groenwold Rolf H H , Dekkers Olaf M
Published: February 2024

For many statistical methods that are commonly used in medical research, it is assumed that observations are independent. However, when this assumption is violated, alternative methods may be needed. In this paper, we describe why an analysis that ignores the dependencies within the data may provide biased results and outline possible alternatives. This paper aims to create awareness among researchers, readers, and reviewers for this possible source of bias in medical research.
Overview of the participation of community health workers in primary health care in 6 Latin American countries and a proposal for their integration into the health system: a qualitative study
Authors: Zuñiga Rosalia Olaya , Parra-García Irene , Gómez-Barrera Luis Alejandro
Published: February 2024

Background

According to some health programmes, implementing primary health care through community health workers (CHWs) facilitates the connection between community and health services in Latin America. However, these are isolated processes that face different obstacles and would benefit from an overview of the corresponding health policies and programmes.

Objective

To provide an overview of CHW participation in 6 Latin American countries.

Methods

This exploratory qualitative study was based on 3 sources of information: a literature review, a review of public health policy documents, and interviews with experts who have led CHW programmes in 6 Latin American countries.

Results

The role of CHWs in Latin America and some advances in public health policies in the region were evidenced. However, limitations arising from variable implementation of the WHO guidelines on health programmes with CHWs were also apparent.

Conclusions

CHWs contribute to the primary healthcare processes in the 6 Latin American countries studied in versatile and comprehensive ways. However, they constitute an underutilized human resource because they must provide various services that are not always relevant in different work contexts. Therefore, we propose a classification of the CHW profile, using the level of access to healthcare services of the population they serve as the main differentiator. This way, CHWs will not have to provide a wide range of services but only those most relevant to the specific needs of each community.
Appraisal of National Institute for Health and Care Research activity in primary care in England: cross-sectional study
Authors: Jonker Leon , Jayne Fisher Stacey
Published: February 2024

Background

The National Institute for Health and Care Research (NIHR) was set up to enhance clinical and health research activity in a variety of National Health Service (NHS) healthcare settings, including primary care.

Objective

To appraise how overall General Practitioner (GP) practice performance, location, and staffing levels may interact with NIHR Portfolio activity in primary care in England.

Methods

Cross-sectional summary of GP practice research activity and practice descriptors; complete data from 6,171 GP practices was collated from NIHR (using data for 2013–2023 for Portfolio studies), Public Health England, Care Quality Commission, and NHS Digital sources, respectively.

Results

In primary care, 1 million patients have been recruited into NIHR Portfolio studies in the last decade. The top 10% of practices—measured by different studies recruited to—contributed over 50% of that accrual. When the top decile of GP practices is compared to the 20% least active GP practices, research activity is significantly and individually linked with larger GP practices. Furthermore, it is significantly yet modestly associated with GP practice performance (positive patient feedback, Care Quality Commission rating), lower locality deprivation levels, and lower patient to GP ratios.

Conclusions

Research activity in GP practices is—as seen previously with hospitals—significantly linked with better GP practice performance and patient feedback. Practice list size and staffing levels in particular interact with the aforementioned. This should be taken into account when determining strategies to increase patient and GP practice participation in NIHR Portfolio research studies.
Insights Into Informal Caregivers’ Well-being: A Longitudinal Analysis of Care Intensity, Care Location, and Care Relationship
Authors: Zhang Yanan , Bennett Matthew R
Published: February 2024

Objectives

This study investigates the psychological well-being of informal caregivers over time. It identifies the thresholds (or “tipping points”) of caring intensity at which caregiving is associated with lower psychological well-being, and how this varies by care location and caregiver–care recipient relationships. It also examines how caring location and relationship are linked to informal caregivers’ psychological well-being while controlling for caring intensity.

Methods

Waves 1–18 (1991–2009) of the harmonized British Household Panel Survey and Waves 1–8 (2009–2017) of the U.K. Household Longitudinal Study were analyzed. Psychological well-being was measured using the General Health Questionnaire (GHQ)-12 score. Care intensity was measured by the weekly hours of care provided. Fixed-effects estimators were applied to the GHQ-12 score of caregivers across different care intensities, caring locations, and caring relationships.

Results

All levels of informal care intensity are associated with lower psychological well-being among spousal caregivers. The thresholds to well-being are 5 hours per week when caring for a parent, and 50 hours per week when caring for a child (with a disability or long-term illness). Caring for “other relatives” or nonrelatives is not negatively associated with psychological well-being. The thresholds are 5 hours per week for both coresident and extraresident caregivers. Extraresident caregivers experience better psychological well-being compared to coresident caregivers, given relatively lower weekly care hours. Caring for primary kin (especially spouses) is linked to lower psychological well-being compared to other caregiving relationships, regardless of care intensity.

Discussion

Policy and practice responses should pay particular attention to spousal caregivers’ well-being. Caregiving relationship has a stronger association with the caregiver’s well-being than care location.
Challenges to correcting pluralistic ignorance: false consensus effects, competing information environments, and anticipated social conflict
Authors: Dixon Graham N , Lerner Blue , Bashian Samuel
Published: February 2024

For many policy issues, people holding the majority opinion often do not act in accordance with their beliefs. While underestimating public opinion appears as a likely cause, correcting this misperception often fails to motivate those in the majority to act. Investigating further, we surveyed a nationally representative sample (N = 1,000) of Republican voters about vaccination. Despite a majority supporting vaccines, Republicans on average underestimated other Republicans’ support. However, this misperception occurred primarily among anti-vaccine Republicans—a group that reported a greater willingness to share their vaccine views. We show how an information environment overrepresented with minority views may discourage majority view holders from speaking out even when they are aware of their majority status. That is, instead of experiencing pluralistic ignorance, those in the majority may be discouraged from expressing their views due to anticipated social conflict from engaging in an information environment disproportionately made up of minority views.
Unravelling collaborative governance dynamics within healthcare networks: a scoping review
Authors: Belrhiti Zakaria , Bigdeli Maryam , Lakhal Aniss , Kaoutar Dib , Zbiri Saad , Belabbes Sanaa
Published: February 2024

In many countries, healthcare systems suffer from fragmentation between hospitals and primary care. In response, many governments institutionalized healthcare networks (HN) to facilitate integration and efficient healthcare delivery. Despite potential benefits, the implementation of HN is often challenged by inefficient collaborative dynamics that result in delayed decision-making, lack of strategic alignment and lack of reciprocal trust between network members. Yet, limited attention has been paid to the collective dynamics, challenges and enablers for effective inter-organizational collaborations. To consider these issues, we carried out a scoping review to identify the underlying processes for effective inter-organizational collaboration and the contextual conditions within which these processes are triggered. Following appropriate methodological guidance for scoping reviews, we searched four databases [PubMed (n = 114), Web of Science (n = 171), Google Scholar (n = 153) and Scopus (n = 52)] and used snowballing (n = 22). A total of 37 papers addressing HN including hospitals were included. We used a framework synthesis informed by the collaborative governance framework to guide data extraction and analysis, while being sensitive to emergent themes. Our review showed the prominence of balancing between top-down and bottom-up decision-making (e.g. strategic vs steering committees), formal procedural arrangements and strategic governing bodies in stimulating participative decision-making, collaboration and sense of ownership. In a highly institutionalized context, the inter-organizational partnership is facilitated by pre-existing legal frameworks. HN are suitable for tackling wicked healthcare issues by mutualizing resources, staff pooling and improved coordination. Overall performance depends on the capacity of partners for joint action, principled engagement and a closeness culture, trust relationships, shared commitment, distributed leadership, power sharing and interoperability of information systems To promote the effectiveness of HN, more bottom-up participative decision-making, formalization of governance arrangement and building trust relationships are needed. Yet, there is still inconsistent evidence on the effectiveness of HN in improving health outcomes and quality of care.
‘Getting control of Corona takes many angles’: COVID-19 vaccine knowledge, attitudes and beliefs among refugee/immigrant/migrant communities in four US cities
Authors: Owen-Smith A , Porter J , Thomas C m , Clarke S , Ogrodnick M m , Hand L J , Dawson-Hahn E , O’Connor M h , Feinberg I , Adde S , Desta R , Yubo Z , Chin A , Safi M
Published: February 2024

The objectives of the study were to (i) document refugee, immigrant and migrant (RIM) communities’ knowledge, attitudes and beliefs (KABs) related to the Coronavirus disease (COVID-19) vaccine and (ii) identify best practices for developing and disseminating culturally and linguistically responsive health messaging addressing those KABs. Thirteen online focus groups (OFGs) in 10 languages were conducted. Each OFG was conducted in the participants’ native language. OFGs were recorded, transcribed, translated and uploaded to qualitative software for coding. A thematic analysis was conducted. Results suggest that while there was some variation between different language groups (e.g. whether religious leaders were seen as trusted sources of information about COVID), there were also important commonalities. Most language groups (i) alluded to hearing about or having gaps in knowledge about COVID-19/the COVID-19 vaccine, (ii) reported hearing negative or conflicting stories about the vaccine and (iii) shared concerns about the negative side effects of the vaccine. There continues to be a need for health messaging in RIM communities that is culturally and linguistically concordant and follows health literacy guidelines. Message content about the COVID-19 vaccine should focus on vaccine importance, effectiveness and safety, should be multimodal and should be primarily delivered by healthcare professionals and community members who have already been vaccinated.
Governments and Markets in the Digital Age
Authors: Calcara Antonio
Published: February 2024

The academic literature has revamped its interest in economic statecraft, geoeconomics, geopoliticization of trade and technology sectors, and in the role of value chains as vectors for exerting control over critical technologies. However, there has been less reflection on state-market relations in the production of technological innovation and on the evolution of government business relations. Four recent books address these two important issues from different angles. Mazzucato and Mallaby’s books focus on the right mix of state and market needed to stimulate technological innovation, and they do so from opposite perspectives. Chen and Ripley’s books look, respectively, at the rise of Tencent as one of China’s major big tech companies and the rise of SpaceX as a key private player in the traditionally state-led US space market. These two books are therefore of interest to gauge the evolving relations between government and private businesses in two key areas of current geopolitical competition, the digital and the space sectors. The aim of this review essay is not only to briefly summarize the content of these books and their strengths and weaknesses, but also to use them as a starting point to reflect on the mix of state and market in the production of innovation, and on government-businesses relations in digital markets.
Incidence of amoxycillin-clavulanic acid associated hepatotoxicity in an Australian children’s hospital
Authors: Eldredge Jessica A , Pittet Laure F , Gwee Amanda
Published: February 2024

Objectives

Amoxycillin/clavulanic acid is the most common antimicrobial cause of drug-induced liver injury in adults. It is a less common cause of severe drug-related hepatotoxicity in children despite its frequent use. We studied the incidence, characteristics and predictive factors for amoxycillin/clavulanic acid hepatoxicity in children.

Design

Retrospective cohort study of children who received oral or intravenous amoxycillin/clavulanic acid at a quaternary children’s hospital over a 5-year period. Children were included if they had liver function tests (LFTs) determined at baseline, during and within 3 months after the treatment course. Causality was assessed using the Naranjo criteria for adverse drug reactions and Roussel Uclaf Causality Assessment Method.

Results

Of 3271 children prescribed amoxycillin/clavulanic acid, 374 were included. Forty-nine (13%) had LFT abnormalities related to amoxycillin/clavulanic acid. Fourteen (3.6%) fulfilled Common Terminology Criteria for Adverse Events (CTCAE) grade 2 criteria with clinically significant hepatotoxicity. Age <2 years, sepsis, post-gastrointestinal surgical indications, prolonged treatment course of >7 days and higher cumulative amoxycillin (>10 g) and clavulanic acid dose (>1 g) were predictive of hepatotoxicity. The median time to resolution of LFT abnormalities was 4 weeks (range 3–7).

Conclusions

The incidence of amoxycillin/clavulanic acid related LFT abnormalities (CTCAE Grade 2 or above) in children was 3.6%. A prolonged treatment course >7 days, high cumulative amoxycillin (10 g) and clavulanic acid (>1 g) doses, those aged <2 years, and patients with sepsis or post-gastrointestinal surgery were predictive of a higher likelihood of abnormal LFTs. LFT monitoring should be considered in children receiving ≥7 days of treatment, particularly in those with other predisposing factors.
Riparin II-type benzamides as novel antibiofilm agents against dermatophytes: chemical synthesis, in vitro, ex vivo and in silico evaluation
Authors: Rocha Marcelo Antônio Nóbrega da , Silva Emanuel Pereira , Silva Risley Nikael Medeiros , Sousa Gabriela Ribeiro de , Barbosa-Filho José Maria , Maia Mayara dos Santos , Lima Alberto Shellygton , de Souza-Ferrari Jailton , Pereira Fillipe de Oliveira
Published: February 2024

Background

The ability of dermatophytes to develop biofilms in host tissues confers physical and biochemical resistance to antifungal drugs. Therefore, research to find new compounds against dermatophyte biofilm is crucial.

Objectives

To evaluate the antifungal activity of riparin II (RIP2), nor-riparin II (NOR2) and dinor-riparin II (DINOR2) against Trichophyton rubrum, Microsporum canis and Nannizzia gypsea strains.

Methods

Initially, we determined the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of benzamides. We evaluated the inhibitory effects on the development of dermatophyte biofilms using in vitro and ex vivo models. Finally, we built three-dimensional models of the sulphite pump Ssu1 to investigate the interactions with the benzamides by molecular docking.

Results

RIP2 showed a broad spectrum of activity against T. rubrum, M. canis and N. gypsea, whereas NOR2 and DINOR2 were more selective. Furthermore, the shortening of the carbon chain from RIP2 benzamide to NOR2 and DINOR2 homologs caused a decrease in the MIC values. The benzamides reduced biofilm production and viability in vitro (P < 0.05) at MIC. This result was similar ex vivo in human nail fragments tests, but NOR2 and DINOR2 showed significant results at 2xMIC (P < 0.05). We constructed a model of the Ssu1 protein for each dermatophyte with high similarity. Molecular docking showed that the benzamides obtained higher binding energy values than ciclopirox.

Conclusions

Our study shows the antibiofilm potential for riparin II-type benzamides as new drugs targeting dermatophytes by inhibiting the Ssu1 protein.
Protein homeostasis and degradation in quiescent neural stem cells
Authors: Kobayashi Taeko
Published: February 2024

Tissue stem cells are maintained in the adult body throughout life and are crucial for tissue homeostasis as they supply newly functional cells. Quiescence is a reversible arrest in the G0/G1 phase of the cell cycle and a strategy to maintain the quality of tissue stem cells. Quiescence maintains stem cells in a self-renewable and differentiable state for a prolonged period by suppressing energy consumption and cell damage and depletion. Most adult neural stem cells in the brain maintain the quiescent state and produce neurons and glial cells through differentiation after activating from the quiescent state to the proliferating state. In this process, proteostasis, including proteolysis, is essential to transition between the quiescent and proliferating states associated with proteome remodeling. Recent reports have demonstrated that quiescent and proliferating neural stem cells have different expression patterns and roles as proteostatic molecules and are affected by age, indicating differing processes for protein homeostasis in these two states in the brain. This review discusses the multiple regulatory stages from protein synthesis (protein birth) to proteolysis (protein death) in quiescent neural stem cells.
The Special Tribunal for Lebanon
Authors: Jurdi Nidal Nabil
Published: February 2024

The article aims to discuss some of the underlying factors that have significantly hindered the ability of the Special Tribunal for Lebanon (STL, or ‘the Tribunal’) to fulfil its mandate — bringing those responsible for the assassination of former Prime Minister Rafik Hariri and others to justice, and thereby bringing justice to victims. Since its inception, the Tribunal has been received with mixed feelings. On the one hand, given the inability and unwillingness of Lebanese domestic courts to deal with gross human rights violations — including heinous terrorist crimes — the establishment of a judicial body was considered indispensable to ending impunity for such crimes. On the other hand, the Tribunal has been perceived as selective and the outcome of a politically-convenient temporary impetus. Adopting a Third World Approach to International Law, the article argues that the model applied in establishing the STL adopted most of the shortcomings of international criminal justice. Furthermore, considering the perceptions of the Tribunal’s legacy among victims and the public in Lebanon and in the wider region, it is no less contentious from a transitional justice perspective. The article concludes that such a model, due to its legal, structural, policy, and management shortcomings, has failed to fulfil its mandate and there are lessons that can be learnt from this contentious experience.
CXCL17 is a proinflammatory chemokine and promotes neutrophil trafficking
Authors: Lowry Emily , Chellappa Rani C , Penaranda Brigith , Sawant Kirti V , Wakamiya Maki , Garofalo Roberto P , Rajarathnam Krishna
Published: February 2024

CXCL17, a novel member of the CXC chemokine class, has been implicated in several human pathologies, but its role in mediating immune response is not well understood. Characteristic features of immune response include resident macrophages orchestrating successive and structured recruitment of neutrophils and monocytes to the insult site. Here, we show that Cxcl17 knockout (KO) mice, compared with the littermate wild-type control mice, were significantly impaired in peritoneal neutrophil recruitment post–lipopolysaccharide (LPS) challenge. Further, the KO mice show dysregulated Cxcl1, Cxcr2, and interleukin-6 levels, all of which directly impact neutrophil recruitment. Importantly, the KO mice showed no difference in monocyte recruitment post–LPS challenge or in peritoneal macrophage levels in both unchallenged and LPS-challenged mice. We conclude that Cxcl17 is a proinflammatory chemokine and that it plays an important role in the early proinflammatory response by promoting neutrophil recruitment to the insult site.
First-trimester uterine rupture in a twin gestation after a motor vehicle collision: a case report
Authors: Cenac Leshae A , Cacciotti Maria , Griffith Tracy
Published: February 2024

Uterine rupture following trauma in pregnancy is rare, especially in earlier gestational ages. The diagnosis can be challenging, and treatment may be delayed when patients present with nonspecific findings. Therefore, a high index of suspicion must be maintained. Once diagnosed, the treatment involves surgical exploration. We present a case report of a first-trimester uterine rupture of a twin pregnancy following a motor vehicle collision in a patient with prior cesarean sections.
Nuclear Cardiology
Authors: Zaret Barry L. , Wackers Frans J. Th.
Published: February 2024

The initial application of radioisotopes to cardiac studies occurred in the mid-1920s to evaluate left ventricular (LV) function. Myocardial stress perfusion imaging was first performed using potassium-43 and exercise in 1973. Stress imaging rapidly evolved thereafter with new tracers (thallium-201 and technetium-99m-labeled agents) and from planar to SPECT approaches. Perfusion imaging rapidly proved its value diagnostically and in assessing prognosis. Advances in hybrid imaging, combining computed tomography CT with radionuclide imaging, haves recently allowed attenuation correction as well as providing the combination of anatomic and physiologic data. PET myocardial perfusion studies have recently become a standard approach for evaluating myocardial perfusion, absolute quantification of coronary blood flow, and coronary flow reserve. PET FDG studies of cardiac sarcoidosis have recently been established as a new approach for defining myocardial inflammation. 10. New cardiac-centered SPECT systems provide high- sensitivity, high-resolution studies, allowing for radiation dose reduction and high-quality imaging studies.
Artifacts
Authors: Decker William A. Van
Published: February 2024

Artifacts are not unique to nuclear cardiac imaging and are observed in many aspects of patient care. All imaging modalities (such as echocardiography, chest x-rays, computed tomography of any type, magnetic resonance imaging, coronary angiography, and electrocardiography) may have artifacts due to the imaging technique. Their recognition and correction improves precision and patient management. With nuclear cardiology, artifacts could be observed with SPECT and PET as well as with radionuclide angiography. The greater number of SPECT studies means that more artifacts are observed with SPECT than PET. Artifacts may affect interpretation of perfusion pattern, LV function, and myocardial blood flow. Artifacts are simply defined as changes in any of the above measurements that are created by the imaging process itself rather than any real biologic or physiologic process. Some are obvious, but others are much more subtle. They could be due to image acquisition, processing, software, hardware, automation, and extracardiac activity. Understanding the causes of the common artifacts will allow recognition of the signature “footprint” on final images. Some artifacts lend themselves to image generation mitigation and others to classic pattern recognition. This chapter will characterize artifacts and explain common ways to manage each for clinically improved interpretation.
Imaging Infection of Valves and Devices
Authors: Schindler Thomas H. , Ghannudi Soraya El , Imperiale Alessio
Published: February 2024

With the increasing success of cardiovascular device implantations, a significant rise in device infections and hospital admissions has occurred. These infections commonly present a diagnostic challenge as echocardiography as a first-line investigation may be limited. Additional imaging with contrast computed tomography (CTA) and/or 18F-FDG PET may provide incremental diagnostic value that may be critical for decision-making. Diagnostic delay may lead to a delay in appropriate treatment and a worsened clinical outcome. Thus, early identification of device infections with the additional use of 18F-FDG PET and/or CTA within a multidisciplinary expert team is important. Despite the promising emergence of 18F-FDG PET in the detection of device infections, the diagnostic challenge to separate postinterventional sterile inflammation from true bacterial infection, in particular within the first 6 months, necessitates a comprehensive assessment of clinical information, the patient’s presentation, microbiological results, the structure and composition of the device, the post-interventional clinical course, and the FDG-uptake pattern. In particular, early postoperative inflammation around the prosthetic valve’s sewing ring may lead to false-positive findings, if not cautiously interpreted in the clinical context. While 18F-FDG PET affords a high sensitivity in identifying device infections, its specificity may be limited given these confounding factors. In such cases, autologous 99mTc-labeled leukocytes SPECT/CT, with its high specificity for detecting infected devices, may be added to optimize the diagnostic yield where 18F-FDG PET may be equivocal. Large-scale, well-elaborated clinical trials are needed to refine and improve the diagnostic accuracy of 18F-FDG PET in the identification and treatment of device infections.
Nuclear Imaging in Patients with Serious Arrhythmias
Authors: Venkatesh Ravi , Malhotra Saurabh
Published: February 2024

Identifying patients who are at risk of serious ventricular arrhythmias continues to remain a challenge, and left ventricular ejection fraction has been shown to be an ineffective predictor of arrhythmic events. Cardiac radionuclide imaging has the ability to image not only myocardial perfusion and function but also myocardial dyssynchrony, innervation/denervation, and metabolism, all of which independently and collectively have been shown to enhance arrhythmic risk prediction. Radionuclide imaging can facilitate substrate-based mapping of arrhythmogenic foci and can aid in planning for and facilitating catheter ablation in patients with recurrent ventricular arrhythmias that have been refractory to medical therapy. This chapter reviews the ability of cardiac radionuclide imaging to stratify arrhythmic risk and to guide device and ablation therapies.
Gastritis and Gastropathy
Authors: Hansel Stephanie L.
Published: February 2024

Inflammation of the stomach can manifest itself as gastritis or gastropathy. Gastritis is a histologic diagnosis referring to inflammatory processes of the stomach. Patients with gastritis may or may not have identifiable endoscopic findings or clinical symptoms. Gastropathy refers to epithelial damage with little or no inflammation. There are several classifications of gastritis and gastropathy. Most of them distinguish between acute and chronic disease and the predominant inflammatory infiltrate seen in biopsy specimens. The etiology of the gastritis or gastropathy is also an important factor in the classification, as is the topography or specific areas of involvement in the stomach.
Complications After Roux-en-Y Surgery
Authors: Gala Khushboo S. , Acosta Andres J.
Published: February 2024

The incidence of obesity continues to increase alarmingly, the burden of disease having tripled since 1975. The prevalence of obesity in the United States was a staggering 42.4% in 2018. There has also been an associated increase in the incidence of obesity-related conditions, including heart disease, stroke, type 2 diabetes, and certain types of cancer. Bariatric surgery is the only effective treatment for severe obesity, resulting in sustained weight loss, improved obesity-associated comorbidities, and reduced mortality. Roux-en-Y gastric bypass remains one of the most popular bariatric procedures. It is extremely effective for weight loss.
Constipation and Fecal Incontinence
Authors: Bharucha Adil E.
Published: February 2024

Colonic functions include the absorption of water and electrolytes, storage of intraluminal contents until elimination is socially convenient, and nutrient salvage from bacterial metabolism of carbohydrates that are not absorbed in the small intestine. The colon absorbs all but 100 mL of fluid and 1 mEq of sodium and chloride from approximately 1,500 mL of chyme received over 24 hours. Absorptive capacity can increase to 5 to 6 L of fluid and 800 to 1,000 mEq of sodium and chloride daily. In a healthy person, the average mouth-to-cecum transit time is approximately 6 hours, and average regional transit times through the right, left, and sigmoid colon are about 12 hours each, with an average total colonic transit time of 36 hours.
Autoimmune Hepatitis
Authors: Eaton John E.
Published: February 2024

Autoimmune hepatitis is a chronic inflammatory disorder of the liver that is associated with formation of autoantibodies, hypergammaglobulinemia, plasma cell infiltrate, and interface hepatitis seen on histologic examination. Autoimmune hepatitis affects patients of all ages and both sexes but occurs more commonly in women (female to male ratio, 3.6:1). The global annual incidence of autoimmune hepatitis ranges from 0.7 to 2 cases per 100,000 persons. Among White people of northern European ancestry, the mean annual incidence of autoimmune hepatitis is 1.9 per 100,000, and the point prevalence is 16.9 per 100,000.
A 74-Year-Old Man With Shortness of Breath, Cough, Rigors, and Malaise
Authors: Raju Mehta Gautam , Daniels Craig E.
Published: February 2024

Hemoptysis is a commonly encountered symptom in patients needing intensive care. Life-threatening hemoptysis is a medical emergency requiring prompt evaluation and treatment.
A 55-Year-Old Woman With Dyspnea, Cough, and Acute Kidney Failure
Authors: Thompson Gwen E. , Specks Ulrich
Published: February 2024

Anti-glomerular basement membrane disease is a pulmonary-renal syndrome characterized by a pathogenic antibody directed against the basement membranes of the glomeruli and alveoli. The result is glomerulonephritis or pulmonary hemorrhage (or both). Diagnosis is based on clinical presentation, serologic markers, and pathologic confirmation. Prognosis is determined from renal factors. Treatment consists of plasma exchange and immunosuppression with glucocorticoids and cyclophosphamide as first-line agents.
An 82-Year-Old Woman With Acute Hypoxic Respiratory Failure
Authors: Herberts Michelle B. , Lau Jessica , Dunn William F.
Published: February 2024

When a patient presents with orthopnea, hypoxia, and muscle weakness, ALS should be considered in the differential diagnosis. Patients usually present with lower extremity weakness but can present with bulbar symptoms or respiratory failure. Complications associated with amyotrophic lateral sclerosis (ALS) include acute hypoxic and hypercapnic respiratory failure that often requires positive pressure ventilation. Noninvasive ventilator support can improve the quality of life and mortality rates of patients with ALS. Sleep-disordered breathing is also common among patients with ALS, and early identification of this disorder is beneficial.
A 74-Year-Old Man With a Pulmonary Nodule and Neck Pain
Authors: Koubek Richard D. , Hoskote Sumedh S.
Published: February 2024

FDG-avid pulmonary nodules with mediastinal or hilar lymph nodes on PET-CT can have malignant or benign origins. Certain characteristics of the nodule appearance and FDG uptake patterns can help guide consideration for a malignant basis in the appropriate clinical context. Non–small cell lung cancer (NSCLC) with ipsiliateral mediastinal lymph node involvement is considered N2 disease and indicates NSCLC that is at least stage IIIA. Treatment of stage III disease is best coordinated with a multidisciplinary team because of the complexity of the decisions involved and the broad spectrum of clinical severity within this stage, but management generally involves platinum-based chemotherapy in combination with radiotherapy.
A 57-Year-Old Woman With Progressively Decreasing Oxygen Saturation After Liver Transplant
Authors: Panda Govind , Patel Bhavesh M.
Published: February 2024

Tension pneumothorax is a life-threatening diagnosis that can be made accurately at the bedside with lung ultrasonography. Treatment consists of emergent needle decompression of the pleural space in the second intercostal space at the midclavicular line or in the fifth intercostal space at the anterior axillary line with a long, large-bore needle and immediate placement of a chest tube.
Broad-band study of gamma-ray blazars at redshifts z = 2.0–2.5
Authors: Sahakyan N , Harutyunyan G , Gasparyan S , Israyelyan D
Published: February 2024

High redshift blazars are among the most powerful non-explosive sources in the Universe and play a crucial role in understanding the evolution of relativistic jets. To understand these bright objects, we performed a detailed investigation of the multiwavelength properties of 79 γ-ray blazars with redshifts ranging from z = 2.0 to 2.5, using data from Fermi LAT, Swift XRT/UVOT, and NuSTAR observations. In the γ-ray band, the spectral analysis revealed a wide range of flux and photon indices, from 5.32 × 10−10 to 3.40 × 10−7 photon cm−2 s−1 and from 1.66 to 3.15, respectively, highlighting the diverse nature of these sources. The detailed temporal analysis showed that flaring activities were observed in 31 sources. Sources such as 4C+71.07, PKS 1329-049, and 4C + 01.02, demonstrated significant increase in the γ-ray luminosity and flux variations, reaching peak luminosity exceeding 1050 erg s−1. The temporal analysis extended to X-ray and optical/ultraviolet (UV) bands, showed clear flux changes in some sources in different observations. The time-averaged properties of high redshift blazars were derived through modeling the spectral energy distributions with a one-zone leptonic scenario, assuming the emission region is within the broad-line region (BLR) and the X-ray and γ-ray emissions are due to inverse Compton scattering of synchrotron and BLR-reflected photons. This modeling allowed us to constrain the emitting particle distribution, estimate the magnetic field inside the jet, and evaluate the jet luminosity, which is discussed in comparison with the disc luminosity derived from fitting the excess in the UV band.
AstroSat and NICER timing view of the Z−type neutron star X-ray binary GX 340 + 0
Authors: Pahari Mayukh , Suman Shree , Bhargava Yash , Weston Alexander , Zhang Liang , Bhattacharyya Sudip , Misra Ranjeev , McHardy Ian
Published: February 2024

The timing properties of the Z-type low-mass X-ray binaries provide insights into the emission components involved in producing the unique Z-shaped track in the hardness–intensity diagrams of these sources. In this work, we investigate the AstroSat and NICER observations of the GX 340 + 0 covering the complete ‘Z’-track from the horizontal branch (HB) to the extended flaring branch (EFB). For the first time, we present the Z-track as seen in soft X-rays using the AstroSat/Soft X-ray Telescope and NICER (the soft colour is defined as a ratio of 3–6 to 0.5–3 keV). The shape of the track is distinctly different in soft X-rays, strongly suggesting the presence of additional components active in soft X-rays. The detailed timing analysis revealed significant quasi-periodic oscillation throughout the HB and the normal branch (NB) using large area X-ray proportional counter and the first NICER detection of 33.1 ± 1.1 Hz HB oscillation (HBO) in 3–6 keV. The oscillations at the HB/NB vertex are observed to have higher frequencies (41–52 Hz) than the HBOs (16–31 Hz) and NB oscillations (6.2–8 Hz) but significantly lower rms (∼1.6 per cent). The HBO is also limited to the energy range 3–20 keV, indicating an association of HBO origin with the non-thermal component. It is also supported by earlier studies that found the strongest X-ray polarization during HB.
The MASSIVE survey – XIX. Molecular gas measurements of the supermassive black hole masses in the elliptical galaxies NGC 1684 and NGC 0997
Authors: Dominiak Pandora , Bureau Martin , Davis Timothy A , Ma Chung-Pei , Greene Jenny E , Gu Meng
Published: February 2024

Supermassive black hole (SMBH) masses can be measured by observing their dynamical effects on tracers, such as molecular gas. We present high angular resolution Atacama Large Millimeter/submillimeter Array observations of the 12CO(2–1) line emission of the early-type galaxies (ETGs) NGC 1684 and NGC 0997, obtained as part of the MASSIVE survey, a volume-limited integral-field spectroscopic study of the most massive local ETGs. NGC 1684 has a regularly rotating central molecular gas disc, with a spatial extent of ≈6 arcsec (≈1.8 kpc) in radius and a central hole slightly larger than the expected SMBH sphere of influence. We forward model the data cube in a Bayesian framework with the Kinematic Molecular Simulation (KinMS) code and infer a SMBH mass of $1.40^{+0.44}_{-0.39}\times 10^9$ M⊙ (3σ confidence interval) and an F110W-filter stellar mass-to-light ratio of (2.50 ± 0.05) M⊙/L⊙, F110W. NGC 0997 has a regularly rotating central molecular gas disc, with a spatial extent of ≈5 arcsec (≈2.2 kpc) in radius and a partially filled central hole much larger than the expected SMBH sphere of influence, thus preventing a robust SMBH mass determination. With the same modelling method, we nevertheless constrain the SMBH mass to be in the range 4.0 × 107–1.8 × 109 M⊙ and the F160W-filter stellar mass-to-light ratio to be (1.52 ± 0.11) M⊙/L⊙, F160W. Both SMBH masses are consistent with the SMBH mass–stellar velocity dispersion (MBH–σe) relation, suggesting that the overmassive SMBHs present in other very massive ETGs are fairly uncommon.
The Three Hundred: Msub–Vcirc relation
Authors: Srivastava Atulit , Cui Weiguang , Meneghetti Massimo , Dave Romeel , Knebe Alexander , Ragagnin Antonio , Giocoli Carlo , Calura Francesco , Despali Giulia , Moscardini Lauro , Yepes Gustavo
Published: February 2024

In this study, we investigate a recent finding based on strong lensing observations, which suggests that the sub-haloes observed in clusters exhibit greater compactness compared to those predicted by ΛCDM simulations. To address this discrepancy, we compare the cumulative sub-halo mass function and the Msub–Vcirc relation between observed clusters and 324 simulated clusters from $\rm \small {The\,Three\,\,Hundred}$ project, focusing on the hydrodynamic resimulations using $\rm \small {Gadget-X}$ and $\rm \small {Gizmo-Simba}$ baryonic models. The cumulative sub-halo mass function of $\rm \small {Gizmo-Simba}$ simulated clusters aligns with observations, while $\rm \small {Gadget-X}$ simulations exhibit discrepancies in the lower sub-halo mass range, possibly due to its strong supernova feedback. Both $\rm \small {Gadget-X}$ and $\rm \small {Gizmo-Simba}$ simulations demonstrate a redshift evolution of the sub-halo mass function and the Vcirc function, with slightly fewer sub-haloes observed at lower redshifts. Neither the $\rm \small {Gadget-X}$ nor $\rm \small {Gizmo-Simba}$ (albeit a little closer) simulated clusters’ predictions for the Msub–Vcirc relation align with the observational result. Further investigations on the correlation between sub-halo/halo properties and the discrepancy in the Msub–Vcirc relation reveal that the sub-halo’s half mass radius and galaxy stellar age, the baryon fraction, and sub-halo distance from the cluster’s centre, as well as the halo relaxation state, play important roles on reproducing this relation. Nonetheless, challenges persist in accurately reproducing the observed Msub–Vcirc relationship within our current hydrodynamic cluster simulation that adheres to the standard ΛCDM cosmology. These challenges may stem from shortcomings in our baryon modelling, numerical intricacies within the simulation, or even potential limitations of the ΛCDM framework.
A jingmenvirus RNA-dependent RNA polymerase structurally resembles the flavivirus counterpart but with different features at the initiation phase
Authors: Wang Xinyu , Jing Xuping , Shi Junming , Liu Qiaojie , Shen Shu , Cheung Peter Pak-Hang , Wu Jiqin , Deng Fei , Gong Peng
Published: February 2024

Jingmenviruses are a category of emerging segmented viruses that have garnered global attention in recent years, and are close relatives of the flaviviruses in the Flaviviridae family. One of their genome segments encodes NSP1 homologous to flavivirus NS5. NSP1 comprises both the methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRP) modules playing essential roles in viral genome replication and capping. Here we solved a 1.8-Å resolution crystal structure of the NSP1 RdRP module from Jingmen tick virus (JMTV), the type species of jingmenviruses. The structure highly resembles flavivirus NS5 RdRP despite a sequence identity less than 30%. NSP1 RdRP enzymatic properties were dissected in a comparative setting with several representative Flaviviridae RdRPs included. Our data indicate that JMTV NSP1 produces characteristic 3-mer abortive products similar to the hepatitis C virus RdRP, and exhibits the highest preference of terminal initiation and shorter-primer usage. Unlike flavivirus NS5, JMTV RdRP may require the MTase for optimal transition from initiation to elongation, as an MTase-less NSP1 construct produced more 4–5-mer intermediate products than the full-length protein. Taken together, this work consolidates the evolutionary relationship between the jingmenvirus group and the Flaviviridae family, providing a basis to the further understanding of their viral replication/transcription process.
Dimeric structures of DNA ATTTC repeats promoted by divalent cations
Authors: Trajkovski Marko , Pastore Annalisa , Plavec Janez
Published: February 2024

Structural studies of repetitive DNA sequences may provide insights why and how certain repeat instabilities in their number and nucleotide sequence are managed or even required for normal cell physiology, while genomic variability associated with repeat expansions may also be disease-causing. The pentanucleotide ATTTC repeats occur in hundreds of genes important for various cellular processes, while their insertion and expansion in noncoding regions are associated with neurodegeneration, particularly with subtypes of spinocerebellar ataxia and familial adult myoclonic epilepsy. We describe a new striking domain-swapped DNA–DNA interaction triggered by the addition of divalent cations, including Mg2+ and Ca2+. The results of NMR characterization of d(ATTTC)3 in solution show that the oligonucleotide folds into a novel 3D architecture with two central C:C+ base pairs sandwiched between a couple of T:T base pairs. This structural element, referred to here as the TCCTzip, is characterized by intercalative hydrogen-bonding, while the nucleobase moieties are poorly stacked. The 5′- and 3′-ends of TCCTzip motif are connected by stem-loop segments characterized by A:T base pairs and stacking interactions. Insights embodied in the non-canonical DNA structure are expected to advance our understanding of why only certain pyrimidine-rich DNA repeats appear to be pathogenic, while others can occur in the human genome without any harmful consequences.
Tet-mediated DNA methylation dynamics affect chromosome organization
Authors: Tian Hao , Luan Pengfei , Liu Yaping , Li Guoqiang
Published: February 2024

DNA Methylation is a significant epigenetic modification that can modulate chromosome states, but its role in orchestrating chromosome organization has not been well elucidated. Here we systematically assessed the effects of DNA Methylation on chromosome organization with a multi-omics strategy to capture DNA Methylation and high-order chromosome interaction simultaneously on mouse embryonic stem cells with DNA methylation dioxygenase Tet triple knock-out (Tet-TKO). Globally, upon Tet-TKO, we observed weakened compartmentalization, corresponding to decreased methylation differences between CpG island (CGI) rich and poor domains. Tet-TKO could also induce hypermethylation for the CTCF binding peaks in TAD boundaries and chromatin loop anchors. Accordingly, CTCF peak generally weakened upon Tet-TKO, which results in weakened TAD structure and depletion of long-range chromatin loops. Genes that lost enhancer–promoter looping upon Tet-TKO showed DNA hypermethylation in their gene bodies, which may compensate for the disruption of gene expression. We also observed distinct effects of Tet1 and Tet2 on chromatin organization and increased DNA methylation correlation on spatially interacted fragments upon Tet inactivation. Our work showed the broad effects of Tet inactivation and DNA methylation dynamics on chromosome organization.