bluuebunny/crossref_metadata_2025 huggingface dataset:
Swift J1644+57 as an off-axis Jet
Authors: Beniamini Paz , Piran Tsvi , Matsumoto Tatsuya
Published: June 2023

One of the intriguing puzzles concerning Swift J1644+57, the first jetted tidal disruption event (TDE) discovered, is the constant increase in its jet energy, as implied by radio observations. During the first two hundred days, the jet energy has increased by an order of magnitude. We suggest that the jet was viewed slightly off-axis. In this case, the apparent energy increase arises due to the slowing down of the jet and the corresponding broadening of its beaming cone. Using equipartition analysis, we infer an increasing jet energy as a larger region of the jet is observed. A simple off-axis model accounts nicely for the multi-wavelength radio observations, resolving this long-standing puzzle. The model allows us to self-consistently evolve the synchrotron signature from an off-axis jet as a function of time. It also allows us to estimate, for the first time, the beaming angle of the jet, θ0 ≈ 21°. Considering existing limits on the black hole mass, ≲107 M⊙, this angle implies that the prompt phase beaming corrected luminosity of Swift J1644+57, ∼1047 ergs sec−1, was super Eddington. We also present a closure relation between the spectral and temporal flux for off-axis jets, which can be used to test whether a given radio transient is off-axis or not.
RNase H1 facilitates recombinase recruitment by degrading DNA–RNA hybrids during meiosis
Authors: Liu Chao , Wang Liying , Li Yanan , Guo Mengmeng , Hu Jun , Wang Teng , Li Mengjing , Yang Zhuo , Lin Ruoyao , Xu Wei , Chen Yinghong , Luo Mengcheng , Gao Fei , Chen Jia-Yu , Sun Qianwen , Liu Hongbin , Sun Bo , Li Wei
Published: June 2023

DNA–RNA hybrids play various roles in many physiological progresses, but how this chromatin structure is dynamically regulated during spermatogenesis remains largely unknown. Here, we show that germ cell-specific knockout of Rnaseh1, a specialized enzyme that degrades the RNA within DNA–RNA hybrids, impairs spermatogenesis and causes male infertility. Notably, Rnaseh1 knockout results in incomplete DNA repair and meiotic prophase I arrest. These defects arise from the altered RAD51 and DMC1 recruitment in zygotene spermatocytes. Furthermore, single-molecule experiments show that RNase H1 promotes recombinase recruitment to DNA by degrading RNA within DNA–RNA hybrids and allows nucleoprotein filaments formation. Overall, we uncover a function of RNase H1 in meiotic recombination, during which it processes DNA–RNA hybrids and facilitates recombinase recruitment.
Alteration of replication protein A binding mode on single-stranded DNA by NSMF potentiates RPA phosphorylation by ATR kinase
Authors: Kang Yujin , Han Ye Gi , Khim Keon Woo , Choi Woo Gyun , Ju Min Kyung , Park Kibeom , Shin Kyeong Jin , Chae Young Chan , Choi Jang Hyun , Kim Hongtae , Lee Ja Yil
Published: June 2023

Replication protein A (RPA), a eukaryotic single-stranded DNA (ssDNA) binding protein, dynamically interacts with ssDNA in different binding modes and plays essential roles in DNA metabolism such as replication, repair, and recombination. RPA accumulation on ssDNA due to replication stress triggers the DNA damage response (DDR) by activating the ataxia telangiectasia and RAD3-related (ATR) kinase, which phosphorylates itself and downstream DDR factors, including RPA. We recently reported that the N-methyl-D-aspartate receptor synaptonuclear signaling and neuronal migration factor (NSMF), a neuronal protein associated with Kallmann syndrome, promotes RPA32 phosphorylation via ATR upon replication stress. However, how NSMF enhances ATR-mediated RPA32 phosphorylation remains elusive. Here, we demonstrate that NSMF colocalizes and physically interacts with RPA at DNA damage sites in vivo and in vitro. Using purified RPA and NSMF in biochemical and single-molecule assays, we find that NSMF selectively displaces RPA in the more weakly bound 8- and 20-nucleotide binding modes from ssDNA, allowing the retention of more stable RPA molecules in the 30-nt binding mode. The 30-nt binding mode of RPA enhances RPA32 phosphorylation by ATR, and phosphorylated RPA becomes stabilized on ssDNA. Our findings provide new mechanistic insight into how NSMF facilitates the role of RPA in the ATR pathway.
dsRNA-induced immunity targets plasmodesmata and is suppressed by viral movement proteins
Authors: Huang Caiping , Sede Ana Rocío , Elvira-González Laura , Yan Yan , Rodriguez Miguel Eduardo , Mutterer Jérôme , Boutant Emmanuel , Shan Libo , Heinlein Manfred
Published: June 2023

Emerging evidence indicates that in addition to its well-recognized functions in antiviral RNA silencing, dsRNA elicits pattern-triggered immunity (PTI), likely contributing to plant resistance against virus infections. However, compared to bacterial and fungal elicitor-mediated PTI, the mode-of-action and signaling pathway of dsRNA-induced defense remain poorly characterized. Here, using multicolor in vivo imaging, analysis of GFP mobility, callose staining, and plasmodesmal marker lines in Arabidopsis thaliana and Nicotiana benthamiana, we show that dsRNA-induced PTI restricts the progression of virus infection by triggering callose deposition at plasmodesmata, thereby likely limiting the macromolecular transport through these cell-to-cell communication channels. The plasma membrane-resident SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE 1, the BOTRYTIS INDUCED KINASE1/AVRPPHB SUSCEPTIBLE1-LIKE KINASE1 kinase module, PLASMODESMATA-LOCATED PROTEINs 1/2/3, as well as CALMODULIN-LIKE 41 and Ca2+ signals are involved in the dsRNA-induced signaling leading to callose deposition at plasmodesmata and antiviral defense. Unlike the classical bacterial elicitor flagellin, dsRNA does not trigger a detectable reactive oxygen species (ROS) burst, substantiating the idea that different microbial patterns trigger partially shared immune signaling frameworks with distinct features. Likely as a counter strategy, viral movement proteins from different viruses suppress the dsRNA-induced host response leading to callose deposition to achieve infection. Thus, our data support a model in which plant immune signaling constrains virus movement by inducing callose deposition at plasmodesmata and reveals how viruses counteract this layer of immunity.
VERNALIZATION1 represses FLOWERING PROMOTING FACTOR1-LIKE1 in leaves for timely flowering in Brachypodium distachyon
Authors: Liu Shu , Chen Siyi , Zhou Yang , Shen Yuxin , Qin Zhengrui , Wu Liang
Published: June 2023

FLOWERING PROMOTING FACTOR1 (FPF1), a small protein without any known domains, promotes flowering in several plants; however, its functional mechanism remains unknown. Here, we characterized 2 FPF1-like proteins, FPL1 and FPL7, which, in contrast, function as flowering repressors in Brachypodium distachyon. FPL1 and FPL7 interact with the components of the florigen activation complex (FAC) and inhibit FAC activity to restrict expression of its critical target, VERNALIZATION1 (VRN1), in leaves, thereby preventing overaccumulation of FLOWERING LOCUS T1 (FT1) at the juvenile stage. Further, VRN1 can directly bind to the FPL1 promoter and repress FPL1 expression; hence, as VRN1 gradually accumulates during the late vegetative stage, FAC is released. This accurate feedback regulation of FPL1 by VRN1 allows proper FT1 expression in leaves and ensures sufficient FAC formation in shoot apical meristems to trigger timely flowering. Overall, we define a sophisticated modulatory loop for flowering initiation in a temperate grass, providing insights toward resolving the molecular basis underlying fine-tuning flowering time in plants.
A machine learning approach to galactic emission-line region classification
Authors: Rhea Carter L , Rousseau-Nepton Laurie , Moumen Ismael , Prunet Simon , Hlavacek-Larrondo Julie , Grasha Kathryn , Robert Carmelle , Morisset Christophe , Stasinska Grazyna , Vale-Asari Natalia , Giroux Justine , McLeod Anna , Gendron-Marsolais Marie-Lou , Wang Junfeng , Lyman Joe , Chemin Laurent
Published: June 2023

Diagnostic diagrams of emission-line ratios have been used extensively to categorize extragalactic emission regions; however, these diagnostics are occasionally at odds with each other due to differing definitions. In this work, we study the applicability of supervised machine-learning techniques to systematically classify emission-line regions from the ratios of certain emission lines. Using the Million Mexican Model database, which contains information from grids of photoionization models using cloudy, and from shock models, we develop training and test sets of emission line fluxes for three key diagnostic ratios. The sets are created for three classifications: classic H ii regions, planetary nebulae, and supernova remnants. We train a neural network to classify a region as one of the three classes defined above given three key line ratios that are present both in the SITELLE and MUSE instruments’ band-passes: [O iii]λ5007/H β, [N ii]λ6583/H α, ([S ii]λ6717+[S ii]λ6731)/H α. We also tested the impact of the addition of the [O ii]λ3726, 3729/[O iii]λ5007 line ratio when available for the classification. A maximum luminosity limit is introduced to improve the classification of the planetary nebulae. Furthermore, the network is applied to SITELLE observations of a prominent field of M33. We discuss where the network succeeds and why it fails in certain cases. Our results provide a framework for the use of machine learning as a tool for the classification of extragalactic emission regions. Further work is needed to build more comprehensive training sets and adapt the method to additional observational constraints.
Making sense of knowledge-brokering organisations: boundary organisations or policy entrepreneurs?
Authors: MacKillop Eleanor , Connell Andrew , Downe James , Durrant Hannah
Published: June 2023

Knowledge-brokering organisations (KBOs) have multiplied in the evidence–policy landscape worldwide, changing how decision-makers are accessing evidence. Yet, we still know little about their emergence and roles. This research helps to understand KBOs and their place in evidence-based policymaking by highlighting the varied work that they do, the relationships they cultivate with policymakers, the complex knowledge-brokering processes they negotiate, and how they establish their credibility in different ways. We build on boundary organisation theory and the concept of policy entrepreneur (PE) (drawn from the multiple streams analysis) to develop a better understanding of KBOs who play multiple roles. By using the PE concept, we bring a greater focus on the politics of brokering. This duality involves them in seeking to provide ‘objective’ evidence while simultaneously determining what counts as evidence for policy and making recommendations for political decisions.
High blood lead levels of children in a gold mining community in Osun State, Nigeria: an urgent call for action
Authors: Akinwumi Ifeoluwa A , Adegoke Samuel A , Oyelami Oyeku A , Akinwumi Abiodun E , Adedeji Tewogbade A
Published: June 2023

Background

Environmental exposure from artisanal gold mining activities is a major risk for high blood lead levels (BLLs) in children. Over the last decade, artisanal gold mining activities have been on a sharp increase in some parts of Nigeria. This study compared BLLs of children in the mining community of Itagunmodi and a 50-km distant non-mining community of Imesi-Ile, Osun State, Nigeria.

Methods

This community-based study investigated 234 apparently healthy children, with 117 each from Itagunmodi and Imesi-Ile. Relevant history, examination and laboratory findings including BLLs were recorded and analysed.

Results

All participants had BLLs above the cut-off value of 5 µg/dl. However, the mean BLL of subjects living in the gold-mining community (24.2±5.3 µg/dl) was significantly higher than for children in the non-mining area of Imesi-Ile (19.5±6.4 µg/dl; p<0.001). Children in the gold mining community were 3.07 times more likely to have a BLL ≥20 µg/dl than those in the non-mining environment (odds ratio [OR] 3.07 [95% confidence interval {CI} 1.79 to 5.2], p<0.001). Similarly, the odds of having a BLL ≥30 µg/dl was 7.84 times more likely among children living in gold mining Itagunmodi than in Imesi-Ile (OR 7.84 [95% CI 2.32 to 26.46], p<0.0001). BLL was not associated with socio-economic and nutritional status of the participants.

Conclusions

In addition to introduction and enforcement of safe mining practices, regular screening for lead toxicity is advocated for children in these communities.
Systemic Nonsteroidal Anti-Inflammatories for Analgesia in Postoperative Critical Care Patients: A Systematic Review and Meta-Analysis of Randomized Control Trials
Authors: Ma Chen Hsiang , Tworek Kimberly B. , Kung Janice Y. , Kilcommons Sebastian , Wheeler Kathleen , Parker Arabesque , Senaratne Janek , Macintyre Erika , Sligl Wendy , Karvellas Constantine J. , Zampieri Fernando G. , Kutsogiannis Demetrios Jim , Basmaji John , Lewis Kimberley , Chaudhuri Dipayan , Sharif Sameer , Rewa Oleksa G. , Rochwerg Bram , Bagshaw Sean M. , Lau Vincent I.
Published: June 2023

OBJECTIVES:

While opioids are part of usual care for analgesia in the ICU, there are concerns regarding excess use. This is a systematic review of nonsteroidal anti-inflammatory drugs (NSAIDs) use in postoperative critical care adult patients.

DATA SOURCES:

We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, trial registries, Google Scholar, and relevant systematic reviews through March 2023.

STUDY SELECTION:

Titles, abstracts, and full texts were reviewed independently and induplicate by two investigators to identify eligible studies. We included randomized control trials (RCTs) that compared NSAIDs alone or as an adjunct to opioids for systemic analgesia. The primary outcome was opioid utilization.

DATA EXTRACTION:

In duplicate, investigators independently extracted study characteristics, patient demographics, intervention details, and outcomes of interest using predefined abstraction forms. Statistical analyses were conducted using Review Manager software Version 5.4. (The Cochrane Collaboration, Copenhagen, Denmark).

DATA SYNTHESIS:

We included 15 RCTs (n = 1,621 patients) for admission to the ICU for postoperative management after elective procedures. Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4 mg (95% CI, 11.8–31.0 mg reduction; high certainty) and probably reduced pain scores (measured by Visual Analog Scale) by 6.1 mm (95% CI, 12.2 decrease to 0.1 increase; moderate certainty). Adjunctive NSAID therapy probably had no impact on the duration of mechanical ventilation (1.6 hr reduction; 95% CI, 0.4 hr to 2.7 reduction; moderate certainty) and may have no impact on ICU length of stay (2.1 hr reduction; 95% CI, 6.1 hr reduction to 2.0 hr increase; low certainty). Variability in reporting adverse outcomes (e.g., gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis.

CONCLUSIONS:

In postoperative critical care adult patients, systemic NSAIDs reduced opioid use and probably reduced pain scores. However, the evidence is uncertain for the duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the prevalence of NSAID-related adverse outcomes.
Angiotensin II for the Treatment of Refractory Shock: A Matched Analysis*
Authors: Smith Lane M. , Mentz Graciela B. , Engoren Milo C.
Published: June 2023

OBJECTIVES:

To determine if angiotensin II is associated with improved outcomes as measured by 30- and 90-day mortality as well as other secondary outcomes such as organ dysfunction and adverse events.

DESIGN:

Retrospective, matched analysis of patients receiving angiotensin II compared with both historical and concurrent controls receiving equivalent doses of nonangiotensin II vasopressors.

SETTING:

Multiple ICUs in a large, university-based hospital.

PATIENTS:

Eight hundred thirteen adult patients with shock admitted to an ICU and requiring vasopressor support.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Angiotensin II use had no association with the primary outcome of 30-day mortality (60% vs 56%; p = 0.292). The secondary outcome of 90-day mortality was also similar (65% vs 63%; p = 0.440) as were changes in Sequential Organ Failure Assessment scores over a 5-day monitoring period after enrollment. Angiotensin II was not associated with increased rates of kidney replacement therapy (odds ratio [OR], 1.39; 95% CI, 0.88–2.19; p = 0.158) or receipt of mechanical ventilation (OR, 1.50; 95% CI, 0.41–5.51; p = 0.539) after enrollment, and the rate of thrombotic events was similar between angiotensin II and control patients (OR, 1.02; 95% CI, 0.71–1.48; p = 0.912).

CONCLUSIONS:

In patients with severe shock, angiotensin II was not associated with improved mortality or organ dysfunction and was not associated with an increased rate of adverse events.
Analysis of Protein Biomarkers From Hospitalized COVID-19 Patients Reveals Severity-Specific Signatures and Two Distinct Latent Profiles With Differential Responses to Corticosteroids*
Authors: Verhoef Philip A. , Spicer Alexandra B. , Lopez-Espina Carlos , Bhargava Akhil , Schmalz Lee , Sims Matthew D. , Palagiri Ashok V. , Iyer Karthik V. , Crisp Matthew J. , Halalau Alexandra , Maddens Nicholas , Gosai Falgun , Syed Anwaruddin , Azad Saleem , Espinosa Aimee , Davila Francisco , Davila Hugo , Evans Neil R. , Smith Scott , Reddy Bobby , Sinha Pratik , Churpek Matthew M.
Published: June 2023

OBJECTIVES:

To identify and validate novel COVID-19 subphenotypes with potential heterogenous treatment effects (HTEs) using electronic health record (EHR) data and 33 unique biomarkers.

DESIGN:

Retrospective cohort study of adults presenting for acute care, with analysis of biomarkers from residual blood collected during routine clinical care. Latent profile analysis (LPA) of biomarker and EHR data identified subphenotypes of COVID-19 inpatients, which were validated using a separate cohort of patients. HTE for glucocorticoid use among subphenotypes was evaluated using both an adjusted logistic regression model and propensity matching analysis for in-hospital mortality.

SETTING:

Emergency departments from four medical centers.

PATIENTS:

Patients diagnosed with COVID-19 based on International Classification of Diseases, 10th Revision codes and laboratory test results.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Biomarker levels generally paralleled illness severity, with higher levels among more severely ill patients. LPA of 522 COVID-19 inpatients from three sites identified two profiles: profile 1 (n = 332), with higher levels of albumin and bicarbonate, and profile 2 (n = 190), with higher inflammatory markers. Profile 2 patients had higher median length of stay (7.4 vs 4.1 d; p < 0.001) and in-hospital mortality compared with profile 1 patients (25.8% vs 4.8%; p < 0.001). These were validated in a separate, single-site cohort (n = 192), which demonstrated similar outcome differences. HTE was observed (p = 0.03), with glucocorticoid treatment associated with increased mortality for profile 1 patients (odds ratio = 4.54).

CONCLUSIONS:

In this multicenter study combining EHR data with research biomarker analysis of patients with COVID-19, we identified novel profiles with divergent clinical outcomes and differential treatment responses.
Design and Implementation of a Leadership Development Program for Early-Stage Investigators: Initial Results
Authors: Bredella Miriam A. , Patel Karan A. , Leyne Maire , Levy Anne S. , Tannous Bakhos A. , Bouxsein Mary L.
Published: June 2023

Leadership skills are essential for a successful career in medical research but are often not formally taught. To address these gaps, we designed a leadership development program for early-stage investigators.

A 9-month virtual program with monthly 2-hour interactive sessions was designed, covering topics such as Leadership in Research, Mentoring, Building Diverse and Inclusive Teams, Managing Conflict, Influencing without Authority, Grant Administration, and Management. An anonymized survey was sent to participants before and after completion of the program, and the results were compared using the chi-squared test.

Over a 2-year period, we selected two cohorts of 41 and 46 participants, respectively. After completion of the program, 92% of survey respondents indicated that the program met their expectations and 74% had made use of skills they learned. Participants enjoyed meeting new people and discussing common challenges. There was an increase in participants' perceived understanding of personal leadership qualities, mentoring, communication, conflict resolution, grant management, and collaboration with industry (P < .05).

A leadership development program for early-stage investigators led to a significant increase in participants' perceived understanding of personal leadership qualities and competencies. It also offered participants the opportunity to meet other researchers in the institution and discuss common challenges.
Cutaneous Lesions of Mastocytosis: Mast Cell Count, Morphology, and Immunomolecular Phenotype
Authors: Damman Jeffrey , Diercks Gilles F.H. , van Doorn Martijn B. , Pasmans Suzanne GMA , Hermans Maud A.W.
Published: June 2023

Mastocytosis is a condition characterized by accumulation of clonal mast cells (MCs) that often involves the skin. Pathologists are often challenged with skin biopsies with a question of cutaneous lesions of mastocytosis (CLM) including cutaneous mastocytosis, mastocytosis in the skin, or systemic mastocytosis. The histopathological criteria for CLM remain poorly defined due to heterogeneity of the published literature and the lack of comparative prospective studies. MC count is greatly influenced by detection and counting techniques, criteria for viable MCs used, anatomical location biopsied, and the dermal level that is analyzed. Although MC numbers in CLM can be significantly higher compared with healthy controls and a patient with other inflammatory skin diseases, in some instances, considerable overlap exists. Based on the largest studies published, it is suggested that a number of MCs between 75 and 250 MCs/mm2 are a range in which CLM should be considered and, above 250 MC/mm2, a diagnosis of CLM can be made. A recent study showed a high specificity of >95% of a MC count >139 MC/mm2 compared with patients with other inflammatory skin diseases. Noteworthy, the total number and percentage of MCs is significantly higher in children compared with adults, particularly in polymorphic maculopapular cutaneous mastocytosis. In difficult cases, ancillary techniques such as D816V mutation analysis on formalin-fixed paraffin-embedded tissue have a high sensitivity and specificity. There is no enough evidence that immunohistochemistry of CD25, CD2, or CD30 has any additional value in the diagnosis, subtyping, or clinical course of mastocytosis.
Merkel Cell Carcinoma In Situ Arising in Association With an Infundibular Cyst With Unusual Reticulated Infundibulocystic Proliferation
Authors: Peralta Isairis , Dacey Elizabeth B. , King Roy
Published: June 2023

Merkel cell carcinoma (MCC) is an uncommon aggressive primary cutaneous neuroendocrine tumor usually arising on sun exposed skin of older patients. Most Merkel cell carcinomas are diagnosed as invasive tumors with only rare cases of MCC in situ (MCCIS) reported. MCCs are often associated with other cutaneous neoplasms and more recently have been described in association with cystic lesions, albeit rarely. We present a unique case of an 80-year-old male with a slow growing nodular lesion on the right buttock that on excision demonstrated MCCIS arising within an infundibular cyst with unusual reticulated infundibulocystic proliferation. The MCCIS was intimately associated with the infundibulocystic proliferation and demonstrated immunopositivity for CK20, CD56, AE1/AE3, synaptophysin, and Merkel cell polyoma virus. The confinement of the MCC to the epithelium together with the Merkel cell polyoma virus positivity further supports the assumption that viral positive MCC may derive from epithelial linage.
Cured HCV patients with suboptimal hepatitis B vaccine response exhibit high self-reactive immune signatures
Authors: Zhou Ming-Ju , Zhang Chao , Fu Yuan-Jie , Wang Haiyan , Ji Yingjie , Huang Xia , Li Lin , Wang Ye , Qing Song , Shi Yanze , Shen Lili , Wang You-Yuan , Li Xiao-Yu , Li Yuan-Yuan , Chen Si-Yuan , Zhen Cheng , Xu Ruonan , Shi Ming , Wang Fu-Sheng , Cheng Yongqian
Published: June 2023

Background and Rationale:

Chronic HCV infection induces lasting effects on the immune system despite viral clearance. It is unclear whether certain immune alterations are associated with vaccine responses in cured HCV patients.

Approach:

Thirteen cured HCV patients received the standard 3-dose hepatitis B vaccine and were followed up at the 0, 1st, 6th, and 7th months (M0, M1, M6, and M7) after the first dose of vaccination. Thirty-three-color and 26-color spectral flow cytometry panels were used for high-dimensional immunophenotyping of the T-cell and B-cell subsets, respectively.

Results:

Compared to the healthy controls (HC), 17 of 43 (39.5%) immune cell subsets showed abnormal frequencies in cured HCV patients. Patients with cured HCV were further divided into high responders (HR, n = 6) and nonresponders (NR1, n = 7) based on the levels of hepatitis B surface antibodies at M1. Alterations in cell populations were more significant in NR1. Moreover, we found that high levels of self-reactive immune signatures, including Tregs, TD/CD8, IgD-only memory B, and autoantibodies, were associated with suboptimal hepatitis B vaccine responses.

Conclusions:

Our data suggest that cured HCV patients exhibit persistent perturbations in the adaptive immune system, among which highly self-reactive immune signatures may contribute to a suboptimal hepatitis B vaccine response.
A System for Rapidly Yet Rigorously Evaluating the Quality of Randomized Controlled Trials
Authors: Smith Eric G. , Grigorian Hannah L.
Published: June 2023

This tutorial describes a system for rapidly yet rigorously assessing the quality of randomized controlled trials (RCTs). The system has 7 criteria, represented by the acronym “BIS FOES.” The BIS FOES system directs readers to assess RCTs based on the following 7 criteria: the RCT's use (or not) of effective (1) Blinding; the RCT's use (or not) of (2) Intent-to-Treat Analysis; the RCT's (3) Size and other information reflecting the effectiveness of randomization; the amount of sample lost during (4) Follow-up; the (5) Outcomes examined by the RCT (specifically, the outcomemeasuresused by the RCT), the (6) Effects reported (ie, the statistical and clinical significance of the RCT's primary, secondary, and safety findings), and any (7) Special Considerations (ie, additional strengths, limitations, or notable features of the RCT). The first 6 criteria are of basic importance to the assessment of every RCT, whereas the Special Considerations criteria allows the system to be expanded to include virtually any other important aspect of the RCT. This tutorial explains the importance of these criteria and how to assess them. This tutorial also describes how many BIS FOES criteria can be initially assessed from the RCT Abstract while also directing readers to specific locations in the RCT article where additional important information can be found. We hope that the BIS FOES system will help healthcare trainees, but also potentially clinicians, researchers, and the general public, rapidly and thoroughly assess RCTs.
The Association Between Female Genital Schistosomiasis and Other Infections of the Lower Genital Tract in Adolescent Girls and Young Women: A Cross-Sectional Study in South Africa
Authors: Shukla Jilna Dilip , Kleppa Elisabeth , Holmen Sigve , Ndhlovu Patricia D. , Mtshali Andile , Sebitloane Motshedisi , Vennervald Birgitte Jyding , Gundersen Svein Gunnar , Taylor Myra , Kjetland Eyrun Floerecke
Published: June 2023

Objectives/Purposes of the Study

This study aimed to explore the relationship between female genital schistosomiasis (FGS), sexually transmitted infections, bacterial vaginosis, and yeast among young women living in Schistosoma haematobium-endemic areas.

Methods

In a cross-sectional study of young women, sexually active, aged 16 to 22 years in rural KwaZulu-Natal, South Africa, in 32 randomly selected rural schools in schistosomiasis-endemic areas, the authors performed gynecological and laboratory investigations, diagnosed FGS and other infections, and did face-to-face interviews.

Results

Female genital schistosomiasis was the second most prevalent current genital infection (23%), significantly more common in those who had urinary schistosomiasis (35%), compared with those without (19%, p < .001). In the FGS-positive group, 35% had human papillomavirus compared with 24% in the FGS-negative group (p = .010). In the FGS-positive group, 37% were seropositive for herpes simplex virus infection, compared with 30% in the FGS-negative group (p = .079). There were significantly fewer chlamydia infections among women with FGS (20%, p = .018) compared with those who did not have FGS (28%).

Conclusions

Female genital schistosomiasis was the second most common genital infection after herpes simplex virus. Human papillomavirus infection was significantly associated with FGS, but Chlamydia was negatively associated with FGS. Women with FGS may have had more frequent contact with the health system for genital discharge. The results show the importance of the inclusion of FGS in the national management protocols for genital infections in areas endemic for S. haematobium and highlight a more comprehensive approach to diagnosis and genital disease management.
Can Concurrent Chemoradiotherapy Add Meaningful Benefit in Addition to Induction Chemotherapy in the Management of Borderline Resectable and Locally Advanced Pancreatic Cancer?
Authors: Saha Animesh , Wadsley Jonathan , Sirohi Bhawna , Goody Rebecca , Anthony Alan , Perumal Karthikeyan , Ulahanan Danny , Collinson Fiona
Published: June 2023

Objectives

The role of concomitant chemoradiotherapy or radiotherapy (RT) after induction chemotherapy (IC) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma is debatable. This systematic review aimed to explore this.

Methods

We searched PubMed, MEDLINE, EMBASE, and Cochrane database. Studies were selected reporting outcomes on resection rate, R0 resection, pathological response, radiological response, progression-free survival, overall survival, local control, morbidity, and mortality.

Results

The search resulted in 6635 articles. After 2 rounds of screening, 34 publications were selected. We found 3 randomized controlled studies and 1 prospective cohort study, and the rest were retrospective studies. There is consistent evidence that addition of concomitant chemoradiotherapy or RT after IC improves pathological response and local control. There are conflicting results in terms of other outcomes.

Conclusions

Concomitant chemoradiotherapy or RT after IC improves local control and pathological response in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. The role of modern RT in improving other outcome requires further research.
Outcomes of Distal Pancreatectomy With Celiac Axis Resection for Pancreatic Cancer
Authors: Shin Dakyum , Hong Sarang , Park Yejong , Kwak Bong Jun , Lee Woohyung , Song Ki Byung , Lee Jae Hoon , Kim Song Cheol , Hwang Dae Wook
Published: June 2023

Objectives

This study aimed to show the clinical and oncologic outcomes of distal pancreatectomy with celiac axis resection (DP-CAR) from a high-volume single center and analyze them from diverse perspectives.

Methods

Forty-eight patients with pancreatic body and tail cancer with celiac axis involvement who underwent DP-CAR were included in the study. The primary outcome was morbidity and 90-day mortality, and the secondary outcome was overall survival and disease-free survival.

Results

Morbidity (Clavien-Dindo classification grade ≥3) occurred in 12 patients (25.0%). Thirteen patients (27.1%) had pancreatic fistula grade B and 3 patients (6.3%) had delayed gastric emptying. The 90-day mortality was 2.1% (n = 1). The median overall survival was 25.5 months (interquartile range, 12.3–37.5 months) and median disease-free survival was 7.5 months (interquartile range, 4.0–17.0 months). During the follow-up period, 29.2% of participants survived for up to 3 years and 6.3% survived for up to 5 years.

Conclusions

Despite its associated morbidity and mortality, DP-CAR should be considered as the only therapeutic option for pancreatic body and tail cancer with celiac axis involvement when carried out on carefully selected patients performed by a highly experienced group.
Breakthrough Symptoms Remain an Unmet Need in Symptomatic Patients With Neuroendocrine Tumors and Carcinoid Syndrome
Authors: Liu Eric , Hoffman Kathleen D. , Murfin Gary , Eccard Hannah
Published: June 2023

Objectives

The aims of the study were to assess the effects of breakthrough carcinoid syndrome symptoms on well-being in neuroendocrine tumor (NET) patients insufficiently controlled on long-acting somatostatin analog (SSA) and to assess patient experience with treatment options, physician communication, and disease information sources.

Methods

This study surveyed US NET patients from 2 online communities, experiencing at least one symptom, by utilizing a 64-item questionnaire.

Results

One hundred patients participated: 73% female, 75% age 56 to 75 years, and 93% White. Primary tumor distribution was as follows: gastrointestinal NET (n = 55), pancreatic NET (n = 33), lung NET (n = 11), and other NET (n = 13). All patients were actively treated with one long-acting SSA and experiencing breakthrough symptoms: diarrhea, flushing, or other (13% experienced one, 30% two, 57% greater than two). More than one third of treated patients experienced carcinoid-related symptoms daily. Sixty percent of respondents reported not having short-acting “rescue” treatment available, impacting well-being though anxiety or depression (45%), trouble exercising (65%), sleeping (57%), employment (54%), and maintaining friendships (43%).

Conclusions

Breakthrough symptoms remain an unmet need, even in treated patients with NETs. Though still relying on physicians, NET patients are now also using the Internet. Improved awareness of optimal SSA use may improve syndrome control.
Risk factors, theoretical models, and biological mechanisms of nonsuicidal self-injury: a brief review
Authors: Yan Huiru , Yue Weihua
Published: June 2023

Nonsuicidal self-injury (NSSI) refers to the direct, deliberate infliction of harm to one’s body tissue without the intention to die. The prevalence of NSSI has increased significantly globally in recent years and has become an important public health problem affecting the health of people, especially adolescents. The occurrence of NSSI in adolescents is the result of the interaction of different factors. Many scholars have proposed various theoretical models to explain the mechanism of NSSI behavior based on previous research on the influencing factors of NSSI. Moreover, advances have been made in genetic and neuroimaging mechanisms related to NSSI. Understanding the genetic and neuroimaging mechanisms of NSSI is important for both describing and treating the disorder. This literature review discusses the progress made on the risk factors, theoretical models, and biological mechanisms of NSSI.
Comparison of Risk and Severity of Helicobacter Pylori Infection in Non-Native Versus US Native Pediatric Patients
Authors: Luo Yan , Fu Yinan , Schwarz Steven , Wallach Thomas
Published: June 2023

Introduction:

Helicobacter pylori (HP) infection is associated with gastritis, peptic ulcer disease (PUD) in the stomach and duodenum, and an increased risk of gastric cancer. The risk of infection, secondary symptoms, and negative outcomes is known to be increased in low- and middle-income countries and vastly less substantial in the United States and Europe. Current North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines recommend endoscopic diagnosis and susceptibility-guided therapy, which is not reflected by current adult guidelines for therapy. In this study, we complete a single-center retrospective review of HP risk by nativity status, as well as the results of the use of standard empiric therapy in HP and PUD patients.

Methods:

We retrospectively reviewed all endoscopies with patients aged 1–21 years with a known nativity status and identified all HP diagnoses. We also completed the classification of Kyoto scores and classified patients as gastritis versus PUD. Treatment records were obtained, as well as downstream documentation of the impact of empiric therapy. HP prevalence and severity were compared between non-native and native US populations.

Results:

In total 332 patients were identified, with 59 HP diagnoses. However, 64 patients were immigrants, and 268 were US natives. Totally 39.1% of all immigrant patients had an endoscopically identified HP infection, compared to only 12.7% of US native patients (P < 0.01, relative risk 3.07). HP severity was worse in immigrant patients (Kyoto score 1.5 versus 0.89; P = 0.008). Empiric high-dose amoxicillin triple therapy was equally effective in reducing symptoms in gastritis versus PUD patients.

Conclusions:

Immigrant patients have a substantially higher risk and severity of HP infection than US natives. Empiric therapy remains highly effective at relieving symptoms. These findings in aggregate suggest that North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines may not adequately serve non-native pediatric patients, with an additional prospective multicenter study needed to confirm. In addition, a prospective study of treatment based on stool antigen tests, as well as a larger prospective study of empiric therapy, may suggest alterations to our approach in line with recent changes to adult Gastroenterology practice.
Factors Associated with Cutaneous Colonization of Mucormycetes in Diabetic and Non-Diabetic Individuals
Authors: Saud Bhuvan , Chand Kajal , Amatya Neetu , Paudel Govinda , Adhikari Saroj , Shrestha Vikram
Published: June 2023

This study was conducted to assess factors associated with cutaneous colonization of Mucormycetes in diabetic and non-diabetic individuals. A total of 800 swab samples (from 200 participants, 100 diabetics and 100 non-diabetics) were collected from four different body sites (forehead, nasal, hand and feet) and fungal isolation, identification and sensitivity tests were performed. Overall, 12.0% of participants had Mucormycetes colonization, with diabetics having 11 times greater colonization rate than the non-diabetic counterpart. The commonest fungal isolate was Mucor spp. followed by Rhizopus spp. Majority of the isolates were resistant to Itraconazole; however, all isolates were sensitive to Amphotericin B. A statistical significant result was seen between profession and Mucormycetes colonized individual (p-value=0.03) with significantly higher colonization in retired people in comparison to businesspersons. A higher risk of colonization demonstrated in older age, lower class status, and prolong time contact with soil.
The Mexican dataset of a repetitive transcranial magnetic stimulation clinical trial on cocaine use disorder patients: SUDMEX TMS
Authors: Angeles-Valdez Diego , Rasgado-Toledo Jalil , Villicaña Viviana , Davalos-Guzman Alan , Almanza Cristina , Fajardo-Valdez Alfonso , Alcala-Lozano Ruth , Garza-Villarreal Eduardo A.
Published: June 2023

Cocaine use disorder (CUD) is a worldwide problem with severe health and socio-economic consequences, which results in behavioral, cognitive, and neurobiological disturbances. Consensus on treatments are still under discussion, however, repetitive transcranial magnetic stimulation (rTMS) has been proposed as a promising treatment for medication-resistant disorders, including substance use disorders. Here, we describe the Mexican dataset of an rTMS clinical trial in patients with CUD (SUDMEX-TMS), a longitudinal dataset of 54 CUD participants (8 female) with five timepoints: baseline (T0), two weeks (T1), three months (T2), six months (T3) follow-up, and twelve months (T4) follow-up. Clinical rTMS treatment consisted of a double-blinded randomized clinical trial (n = 24 sham/30 active) for 2 weeks and open label afterwards, and includes demographic, clinical, and cognitive measures, as well as magnetic resonance imaging (MRI) acquisition in all timepoints: 1) structural (T1-weighted), 2) functional (resting state fMRI), and 3) multishell high-angular resolution diffusion-weighted (DWI-HARDI) sequences. The present dataset could be used to examine the impact of rTMS on CUD participants in clinical, cognitive, and multimodal MRI metrics in a longitudinal design.
Cognitive reserve in ALS: The role of occupational skills and requirements
Authors: Rhodes Emma , Alfa Sebleh , Jin Hannah , Massimo Lauren , Elman Lauren , Amado Defne , Baer Michael , Quinn Colin , McMillan Corey T.
Published: June 2023

Background

Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor decline and cognitive impairment. We test the hypothesis that cognitive reserve (CR), defined by occupational histories involving more complex cognitive demands, may protect against cognitive decline, while motor reserve (MR), defined by working jobs requiring complex motor skills, may protect against motor dysfunction.

Methods

Individuals with ALS (n=150) were recruited from the University of Pennsylvania’s Comprehensive ALS Clinic. Cognitive performance was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), and motor functioning was measured using Penn Upper Motor Neuron (PUMNS) scale and ALS Functional Rating Scales (ALSFRS-R). The Occupational Information Network (O*NET) Database was used to derive 17 factors representing distinct worker characteristics, occupational requirements, and worker requirements, which were related to ECAS, PUMNS, and ALSFRS-R scores using multiple linear regression.

Results

A history of working jobs involving greater reasoning ability (β=2.12, p<.05), social ability (β=1.73, p<.05), analytic skills, (β=3.12, p<.01) and humanities knowledge (β=1.83, p<.01) was associated with better performance on the ECAS, while jobs involving more exposure to environmental hazards (β=-2.57, p<.01) and technical skills (β=-2.16, p<.01) were associated with lower ECAS Total Scores. Jobs involving greater precision skills (β=1.91, p<.05) were associated with greater disease severity on the PUMNS. Findings for the ALSFRS-R did not survive correction for multiple comparisons.

Discussion

Jobs requiring greater reasoning abilities, social skills, and humanities knowledge were related to preserved cognitive functioning consistent with CR, while jobs with greater exposure to environmental hazards and technical demands were linked to poorer cognitive functioning. We did not find evidence of MR as no protective effects of occupational skills and requirements were found for motor symptoms, and jobs involving greater precision skills and reasoning abilities were associated with worse motor functioning. Occupational history provides insight into protective and risk factors for variable degrees of cognitive and motor dysfunction in ALS.
COVID-19 Impact in Crohn’s Disease Patients Underwent Autologous Hematopoietic Stem Cell Transplantation
Authors: Ruiz Milton Artur , Kaiser Junior Roberto Luiz , Piron-Ruiz Lilian , Pinho Tainara Souza , Castiglioni Lilian , de Quadros Luiz Gustavo
Published: June 2023

SARS COV 2 is the virus responsible for COVID-19, a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases.

Crohn’s disease (CD) is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota. Patients who underwent Hematopoietic Stem cell Transplantation are considered at risk for COVID-19.

The objective of this report was to describe for the first time the impact of COVID-19 in a group of 50 patients with Crohn’s Disease (CD, 28 females, and 22 male) with a mean age of 38 years, previously submitted to Autologous, non-myeloablative, Hematopoietic Stem Cell Transplantation (Auto HSCT) between 2013 and 2021. In this series, 19 patients were diagnosed with positive COVID-19. In two (2) patients there was a report of the occurrence of two infectious episodes. Parameters related to HSCT, such as time elapsed since the procedure, vaccination status, CD status before and after infection, and clinical manifestations resulting from COVID-19, were evaluated. Among the patients with COVID-19, in three, submitted to Auto HSCT less than six (6) months ago, there was a change in the CD status, and one of them, in addition to the CD symptoms, started to present thyroid impairment with positive anti-TPO. Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission. Nine patients reported late symptoms that may be related to COVID-19. There were no deaths, and the statistical evaluation of the series of COVID-19 patients after HSCT and those who did not present an infectious episode did not present significant data regarding the analyzed parameters. Despite the change in CD status in three patients and the presence of nine patients with late symptoms, we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD.