bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating health services for sexual and gender minorities in France: a qualitative study protocol
Authors: Girard Gabriel , Marsicano Elise , Beaubatie Emmanuel , Eched Yael , Le Bris Mona , Porée Lydie , Raz Michal , Virole Louise 
Published: April 2023

IntroductionDiscrimination and structural violence experienced by sexual and gender minorities are the source of social inequalities in health. The last decade has been marked by major developments in the provision of sexual health services for these minorities in France. This paper presents the research protocol of the Services for Minorities-Lesbian Gays Bisexuals Transgender Intersex+ (SeSAM-LGBTI+) study, which aims to document the health, social and professional challenges in the organisation of current health services for sexual and gender minorities in France.Methods and analysisThe SeSAM-LGBTI+ study relies on a multidisciplinary qualitative study. It has two objectives: (1) to analyse the history of the development of LGBTI+ health services in France, through interviews with key informants and rights activists and through a study of archives and (2) to study the functioning and challenges of a sample of health services currently offered to LGBTI+ people in France, through a multiple case study, using a multilevel and multisited ethnography. The study will rely on approximately 100 interviews. The analysis will be based on an inductive and iterative approach, combining sociohistorical data and the cross-sectional analysis of the case studies.Ethics and disseminationThe study protocol has undergone a peer review by the Institut de Recherche En santé Publique’s scientific committee and has been approved by the research ethical committee of Aix-Marseille University (registration number: 2022-05-12-010). The project has received funding from December 2021 to November 2024. The results of the research will be disseminated from 2023 onwards to researchers, health professionals and community health organisations.
UK medical students’ mental health during the COVID-19 pandemic: a qualitative interview study
Authors: Rich Antonia , Viney Rowena , Silkens Milou , Griffin Ann , Medisauskaite Asta 
Published: April 2023

ObjectivesTo understand the impact of COVID-19 on medical students with mental health problems.DesignQualitative study employing in-depth semistructured interviews with medical students which were analysed using reflexive thematic analysis.Setting and participantsA purposive sample of 20 students originating from 8 geographically spread UK medical schools were selected, representing various mental health issues and demographic characteristics.ResultsThree themes were identified: (1) medical schools’ response to the pandemic—schools increased awareness-raising of mental health support and increased flexibility in regards to academic requirements; (2) disruption to the medical degree—COVID-19 brought change and uncertainty to medical education and missed learning opportunities reduced students’ confidence and (3) psychological consequences of the pandemic—COVID-19 had a negative impact on mental health, most notably raising stress and anxiety but also triggering new or existing conditions.ConclusionsWhile there were many negative aspects of the pandemic for medical students experiencing mental ill health, there were also positives. Students felt that the increased focus on mental health support during the pandemic had reduced stigma towards mental health. Given stigma has been identified as a key barrier for help-seeking in medical students, future research should investigate the longer-term impacts of the pandemic and whether medical students are more likely to seek help for mental health difficulties postpandemic.
Perspectives of individuals on reducing meat consumption to mitigate climate change: protocol for a scoping review
Authors: Moosburger Ramona , Wagner Julia , Heldt Katharina , Richter Almut , Manz Kristin , Mensink Gert B M , Loss Julika 
Published: April 2023

IntroductionHigh consumption of red and processed meat increases the risk of several chronic diseases. Many people, especially in high-income countries, eat more meat than recommended by nutritional and health agencies. Meat production also has negative impacts on the environment and contributes to climate change. Therefore, climate protection, besides health or animal welfare, could motivate individuals to eat less meat. Willingness to reduce meat consumption and motives to do so are not yet fully understood.Methods and analysisBased on the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) extended guidelines, a scoping review of peer-reviewed original studies will be conducted to address three questions: What is the evidence regarding (1) the willingness of individuals to reduce meat consumption to mitigate climate change, (2) the awareness of individuals about the link between their meat consumption and the potential to mitigate climate change and (3) individuals having reduced meat consumption for the reason of climate protection? We will search the databases Medline (via PubMed), Scopus, Embase, Greenfile (via Ebsco) and PsynDex/CurrentContent/Agris (via Livivo) using a systematic search string. Studies from 2015 onwards, published in English, German, Danish or Dutch, will be included. We will include observational studies, qualitative studies, intervention studies (if they include surveys) and reviews. Data will be summarised in a narrative synthesis, comprising methods, population characteristics, meat type under study, indicators measured and limitations. Key findings will be grouped according to the research questions. This scoping review will help clarify the role of climate protection in individual reduction of meat consumption and identify research gaps in this field.Ethics and disseminationFormal ethical approval is not required, as primary data will not be collected in this study. Findings of this scoping review will be presented at scientific conferences and published in a peer-reviewed journal.Trial registration numberhttps://doi.org/10.17605/OSF.IO/MWB85.
Sleep apnoea and hypoventilation in patients with five major types of muscular dystrophy
Authors: Li Leping , Umbach David M , Li Yuanyuan , Halani Pallav , Shi Min , Ahn Mihye , Yeung Deryck S C , Vaughn Bradley , Fan Zheng Jane 
Published: April 2023

BackgroundThe characteristics of and relationship between sleep apnoea and hypoventilation in patients with muscular dystrophy (MD) remain to be fully understood.MethodsWe analysed 104 in-laboratory sleep studies of 73 patients with MD with five common types (DMD—Duchenne, Becker MD, CMD—congenital, LGMD—limb-girdle and DM—myotonic dystrophy). We used generalised estimating equations to examine differences among these types for outcomes.ResultsPatients in all five types had high risk of sleep apnoea with 53 of the 73 patients (73%) meeting the diagnostic criteria in at least one study. Patients with DM had higher risk of sleep apnoea compared with patients with LGMD (OR=5.15, 95% CI 1.47 to 18.0; p=0.003). Forty-three per cent of patients had hypoventilation with observed prevalence higher in CMD (67%), DMD (48%) and DM (44%). Hypoventilation and sleep apnoea were associated in those patients (unadjusted OR=2.75, 95% CI 1.15 to 6.60; p=0.03), but the association weakened after adjustment (OR=2.32, 95% CI 0.92 to 5.81; p=0.08). In-sleep average heart rate was about 10 beats/min higher in patients with CMD and DMD compared with patients with DM (p=0.0006 and p=0.02, respectively, adjusted for multiple testing).ConclusionSleep-disordered breathing is common in patients with MD but each type has its unique features. Hypoventilation was only weakly associated with sleep apnoea; thus, high clinical suspicion is needed for diagnosing hypoventilation. Identifying the window when respiratory muscle weakness begins to cause hypoventilation is important for patients with MD; it enables early intervention with non-invasive ventilation—a therapy that should both lengthen the expected life of these patients and improve its quality.Cite Now
Hospital-level variation in practices and outcomes for patients with severe acute exacerbations of idiopathic pulmonary fibrosis: a retrospective multicentre cohort study
Authors: Shankar Divya A , Walkey Allan J , Hawkins Finn J , Bosch Nicholas A , Peterson Daniel , Law Anica C 
Published: April 2023

BackgroundIn the absence of evidence-based strategies to improve patient outcomes, the management of patients with severe idiopathic pulmonary fibrosis (IPF) exacerbations may vary widely across centres. We assessed between-hospital variation in practices and mortality for patients with severe IPF exacerbations.MethodsUsing the Premier Healthcare Database from 1 October 2015 to 31 December 2020, we identified patients admitted to intensive care unit (ICU) or intermediate care unit with an IPF exacerbation. We assessed idiosyncratic, between-hospital variation in ICU practices (invasive mechanical ventilation (IMV), non-invasive mechanical ventilation (NIMV), corticosteroid use, and immunosuppressive and/or antioxidant use) and hospital mortality by determining median risk-adjusted hospital rates and intraclass correlation coefficients (ICCs) from hierarchical multivariable regression models. A priori, an ICC>15% was deemed ‘high variation’.ResultsWe identified 5256 critically ill patients with a severe IPF exacerbation at 385 US hospitals. Hospital median risk-adjusted rates of practices were: IMV (14% (IQR: 8.3%–26%)), NIMV (42% (31%–54%)), corticosteroid use (89% (84%–93%)), and immunosuppressive and/or antioxidant use (3.3% (1.9%–5.8%)). Model ICCs were: IMV (19% (95% CI: 18% to 21%)), NIMV (15% (13% to 16%)), corticosteroid use (9.8% (8.3% to 11%)), and immunosuppressive and/or antioxidant use (8.5% (7.1% to 9.9%)). The median risk-adjusted hospital mortality was 16% (IQR: 11%–24%) with an ICC of 7.5% (95% CI: 6.2% to 8.9%).InterpretationWe observed high variation in the use of IMV and NIMV, and less variation in corticosteroid and immunosuppressant and/or antioxidant use among patients hospitalised with severe IPF exacerbations. Further research is needed to guide the decisions surrounding initiation of IMV and role of NIMV and to understand the effectiveness of corticosteroids among patients with severe IPF exacerbations.
Alternate-day fasting induces metabolic and morphofunctional changes in the gastrointestinal tract of male rats
Authors: Beckmann Ana Paula Simões , Gama Loyane Almeida , Machado Mariana Pirani Rocha , Alves Wellington David Luz , Corá Luciana Aparecida , Américo Madileine Francely 
Published: April 2023

Alternate-day fasting (ADF) is a nutritional intervention with modulatory and overall protective effects, but its role in the gastrointestinal (GI) tract is still uncertain. The aim of this study was to investigate the influence of ADF on the metabolic patterns and morphofunctional motility of the GI tract in rats. Thirty-two male Wistar rats were allocated into groups: control for 15 days (CON 15, n = 8), control for 30 days (CON 30, n = 8), ADF for 15 days (ADF 15, n = 8), and ADF for 30 days (ADF 30, n = 8). Blood glucose, body weight, and food and water consumption were measured. Frequency and amplitude of gastric contractions as well as gastric emptying time, small intestinal transit time, and cecum arrival time were measured. Intestinal histomorphometric, relative weight of organs, lipidogram, and leptin levels were also evaluated. ADF decreased water consumption and food consumption. The weight gain decreased; however, the relative kidney weight increased. ADF triggered an increase in the amplitude of gastric contractions and accelerated gastric emptying. However, small intestinal transit time was delayed in both ADF groups. Total cholesterol, triglycerides, non-HDL cholesterol, and very low-density lipoprotein cholesterol levels decreased, whereas villus height, depth of the crypts and thickness of the circular, and longitudinal muscular layers of intestine increased after ADF. In conclusion, our results showed ADF exert an effect on both metabolism and GI motility and impacts on overall digestive functions.
Flavour bounds on the flavon of a minimal and a non-minimal $${\mathcal {Z}}_2 \times {\mathcal {Z}}_N$$ symmetry
Authors: Abbas Gauhar , Singh Vartika , Singh Neelam , Sain Ria 
Published: April 2023

AbstractWe investigate flavour bounds on the $${\mathcal {Z}}_2 \times {\mathcal {Z}}_5$$

Z
2

×

Z
5

and $${\mathcal {Z}}_2 \times {\mathcal {Z}}_9$$

Z
2

×

Z
9

flavour symmetries. These flavour symmetries are a minimal and a non-minimal forms of the $${\mathcal {Z}}_2 \times {\mathcal {Z}}_N$$

Z
2

×

Z
N

flavour symmetry, that can provide a simple set-up for the Froggatt–Nielsen mechanism. The $${\mathcal {Z}}_2 \times {\mathcal {Z}}_5$$

Z
2

×

Z
5

and $${\mathcal {Z}}_2 \times {\mathcal {Z}}_9$$

Z
2

×

Z
9

flavour symmetries are capable of explaining the fermionic masses and mixing pattern of the standard model including that of the neutrinos. The bounds on the parameter space of the flavon field of the $${\mathcal {Z}}_2 \times {\mathcal {Z}}_5$$

Z
2

×

Z
5

and $${\mathcal {Z}}_2 \times {\mathcal {Z}}_9$$

Z
2

×

Z
9

flavour symmetries are derived using the current quark and lepton flavour physics data and future projected sensitivities of quark and lepton flavour effects. The strongest bounds on the flavon of the $${\mathcal {Z}}_2 \times {\mathcal {Z}}_5$$

Z
2

×

Z
5

symmetry come from the $$D^0 - {{\bar{D}}}^0$$

D
0

-

D

¯

0

mixing. The bounds on the $${\mathcal {Z}}_2 \times {\mathcal {Z}}_9$$

Z
2

×

Z
9

flavour symmetry are stronger than that of the minimal $${\mathcal {Z}}_2 \times {\mathcal {Z}}_5$$

Z
2

×

Z
5

symmetry. The ratio $$R_{\mu \mu }$$

R

μ
μ

provides rather robust bounds on the flavon parameters in the future phase-I and phase-II of the LHCb by leaving only a very small region in the allowed parameter space of the models.
Formulation and Nutritional Characterization of Mustard and Sesame Oilseed Cake Extract-Based Functional Drinks
Authors: Usman Ifrah , Imran Ali , Arshad Muhamad Umair , Saeed Farhan , Afzaal Muhammad , Sana Saima , Islam Fakhar , Ahmed Aftab , Azam Iqra , Shah Mohd Aisf , Islam Saiful 
Published: April 2023

The current investigation was carried out to develop polyphenol-enriched functional drinks from oil industry waste. Purposely, polyphenols were extracted from the mustard and sesame oilseed cakes through ultrasound-aided extraction alongside conventional extraction mode for comparison purposes. Among the oilseed cake extracts, sesame with methanol and ultrasonic extraction exhibited best results for TPC, DPPH, FRAP, ABTS, and β-carotene as

39
±
0.04

g

GAE/100 g,

35
±
0.02

g

TE/100 g,

20
±
0.02

g

TE/100 g,

18
±
0.03

g

TE/100 g, and

35
±
0.05

g

TE/100 g, respectively, and mustard showed

31
±
0.04

g

GAE/100 g,

20
±
0.01

g

TE/100 g,

16
±
0.02

g

TE/100 g,

12
±
0.01

g

TE/100 g, and

30
±
0.05

g

TE/100 g, respectively. In case of conventional extraction and methanol as solvent, sesame revealed outcomes for TPC, DPPH, FRAP, ABTS, and β-carotene as

13
±
0.02

g

GAE/100 g,

17
±
0.03

g

TE/100 g,

10
±
0.01

g

TE/100 g,

21
±
0.04

g

TE/100 g, and

15
±
0.03

g

TE/100 g, respectively, compared to mustard which showed for TPC, DPPH, FRAP, ABTS, and β-carotene as

11
±
0.02

,

12
±
0.01

,

08
±
0.01

,

17
±
0.03

, and

10
±
0.01

, respectively. Likewise, for mustard oilseed cake extract with conventional extraction technique and water as solvent, minimum findings were observed for TPC, DPPH, FRAP, ABTS, and β-carotene as

07
±
0.01

,

09
±
0.02

,

06
±
0.01

,

14
±
0.03

, and

07
±
0.01

, respectively. T0 without extracts, T1 (sesame oilseed cake extract based Functional drink) , and T2 (mustard oilseed cake extract based Functional drink). The recorded values for total phenols, total flavonoids, total carotenoids, and vitamin C in T0, T1, and T2 were

29.79
±
6.05

,

32.53
±
7.05

, and

30.5
±
5.05

;

26.33
±
5.05

,

30.60
±
7.05

, and

29.75
±
5.05

;

2.11
±
0.05

,

2.12
±
0.05

, and

2.08
±
0.01

; and

31.7
±
7.05

,

30.5
±
5.05

, and

29.6
±
6.05

, respectively. Likewise, sensory evaluation for color, flavor, sweetness, sourness, and overall acceptability during 2 months of storage depicted acceptable scores. The inclusive best outcomes for phytochemical analysis were achieved with sesame oilseed cake extracts by applying ultrasonic extraction technique and methanol as solvent. In the same way, among the developed functional drinks, T1 (sesame oilseed cake extract-based functional drink) exhibited best physiochemical as well as storage characteristics.
Measuring the Impact of Social Media on Young People’s Mental Health: Development and Validation of the Social Media-Induced Tendency Scale
Authors: Ugwu Lawrence Ejike , Idemudia Erhabor Sunday , Chukwu Olive O. , Onyedibe Maria Chidi Christiana 
Published: April 2023

Social media use has been linked to adverse health outcomes such as depression. To facilitate interventions, understanding the varied causes of depression is necessary. The authors developed a social media-induced depression tendency (SMIDT) scale for use with young people and aimed to validate it for young people in Nigeria. The study was conducted in three parts using an online survey (Google Forms) with purposive sampling targeting young people. Study 1 was an exploratory study that developed the SMIDT scale with 361 young people aged 16 to 26 years (

mean

age
=
22.81

). A concise measure of SMIDT was obtained. In study 2, confirmatory factor analysis was performed on the SMIDT with young people aged 17 to 25 years (

mean

age
=
23.61

). Construct, discriminant, and concurrent validities were established, and three factors were identified (sensitivity/attention seeking, worthlessness, and escapism/reality avoidance), which explained 55.87% of the variance. Study 3 tested the predictive validity of the scale. The results showed that the 15-item SMIDT scale had high internal consistency and satisfactory validity. The SMIDT scale can enable the assessment of factors associated with social media-induced depression tendency. The three factors identified in the scale provide insight into the factors contributing to depression associated with social media use. The SMIDT scale has the potential to help identify at-risk individuals and in-developing interventions to prevent or reduce social media-induced depression tendencies. However, this study only focused on young people in Nigeria. Additional studies using the SMIDT scale are required to assess its generalizability and applicability in evaluating other factors, such as quality of life among young people. Moreover, while social media use has been associated with adverse health outcomes, it is crucial to recognize that it can also positively affect mental health. Further research is necessary to explore the complex relationships between social media use and mental health outcomes.
BCA101 Is a Tumor-Targeted Bifunctional Fusion Antibody That Simultaneously Inhibits EGFR and TGFβ Signaling to Durably Suppress Tumor Growth
Authors: Boreddy Srinivas Reddy , Nair Reshmi , Pandey Prashant Kumar , Kuriakose Anshu , Marigowda Shivakumar Bhadravathi , Dey Chaitali , Banerjee Arindam , Kulkarni Hanumant , Sagar Milind , Krishn Shiv Ram , Rao Shruthi , AR Madhukara , Tiwari Vinita , Alke Bhavna , MV Prashantha Kumar , Shri Meena , Dhamne Chaitrali , Patel Sonal , Sharma Pinky , Periyasamy Sankar , Bhatnagar Jaya , Kuriakose Moni Abraham , Reddy Ram Bhupal , Suresh Amritha , Sreenivas Suma , Govindappa Nagaraja , Moole Praveen Reddy , Bughani Usha , Tan Seng-Lai , Nair Pradip 
Published: April 2023

Abstract

The EGFR and TGFβ signaling pathways are important mediators of tumorigenesis, and cross-talk between them contributes to cancer progression and drug resistance. Therapies capable of simultaneously targeting EGFR and TGFβ could help improve patient outcomes across various cancer types. Here, we developed BCA101, an anti-EGFR IgG1 mAb linked to an extracellular domain of human TGFβRII. The TGFβ “trap” fused to the light chain in BCA101 did not sterically interfere with its ability to bind EGFR, inhibit cell proliferation, or mediate antibody-dependent cellular cytotoxicity. Functional neutralization of TGFβ by BCA101 was demonstrated by several in vitro assays. BCA101 increased production of proinflammatory cytokines and key markers associated with T-cell and natural killer–cell activation, while suppressing VEGF secretion. In addition, BCA101 inhibited differentiation of naïve CD4+ T cells to inducible regulatory T cells (iTreg) more strongly than the anti-EGFR antibody cetuximab. BCA101 localized to tumor tissues in xenograft mouse models with comparable kinetics to cetuximab, both having better tumor tissue retention over TGFβ “trap.” TGFβ in tumors was neutralized by approximately 90% in animals dosed with 10 mg/kg of BCA101 compared with 54% in animals dosed with equimolar TGFβRII-Fc. In patient-derived xenograft mouse models of head and neck squamous cell carcinoma, BCA101 showed durable response after dose cessation. The combination of BCA101 and anti-PD1 antibody improved tumor inhibition in both B16-hEGFR–expressing syngeneic mouse models and in humanized HuNOG-EXL mice bearing human PC-3 xenografts. Together, these results support the clinical development of BCA101 as a monotherapy and in combination with immune checkpoint therapy.

Significance:
The bifunctional mAb fusion design of BCA101 targets it to the tumor microenvironment where it inhibits EGFR and neutralizes TGFβ to induce immune activation and to suppress tumor growth.
Novel BCL-2 Inhibitor Lisaftoclax in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematologic Malignancies: First-in-Human Open-Label Trial
Authors: Ailawadhi Sikander , Chen Zi , Huang Bo , Paulus Aneel , Collins Mary C. , Fu Lei (Tommy) , Li Mingyu , Ahmad Mohammad , Men Lichuang , Wang Hengbang , Davids Matthew S. , Liang Eric , Mekala Divya J. , He Zhicong , Lasica Masa , Yannakou Costas K. , Parrondo Ricardo , Glass Laura , Yang Dajun , Chanan-Khan Asher , Zhai Yifan 
Published: April 2023

Abstract

Purpose:
This global phase I trial investigated the safety, efficacy, pharmacokinetics, and pharmacodynamics of lisaftoclax (APG-2575), a novel, orally active, potent selective B-cell lymphoma 2 (BCL-2) inhibitor, in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies (HMs).

Patients and Methods:
Maximum tolerated dose (MTD) and recommended phase II dose were evaluated. Outcome measures were safety and tolerability (primary) and pharmacokinetic variables and antitumor effects (secondary). Pharmacodynamics in patient tumor cells were explored.

Results:
Among 52 patients receiving lisaftoclax, MTD was not reached. Treatment-emergent adverse events (TEAEs) included diarrhea (48.1%), fatigue (34.6%), nausea (30.8%), anemia and thrombocytopenia (28.8% each), neutropenia (26.9%), constipation (25.0%), vomiting (23.1%), headache (21.2%), peripheral edema and hypokalemia (17.3% each), and arthralgia (15.4%). Grade ≥ 3 hematologic TEAEs included neutropenia (21.2%), thrombocytopenia (13.5%), and anemia (9.6%), none resulting in treatment discontinuation. Clinical pharmacokinetic and pharmacodynamic results demonstrated that lisaftoclax had a limited plasma residence and systemic exposure and elicited rapid clearance of malignant cells. With a median treatment of 15 (range, 6–43) cycles, 14 of 22 efficacy-evaluable patients with R/R CLL/SLL experienced partial responses, for an objective response rate of 63.6% and median time to response of 2 (range, 2–8) cycles.

Conclusions:
Lisaftoclax was well tolerated, with no evidence of tumor lysis syndrome. Dose-limiting toxicity was not reached at the highest dose level. Lisaftoclax has a unique pharmacokinetic profile compatible with a potentially more convenient daily (vs. weekly) dose ramp-up schedule and induced rapid clinical responses in patients with CLL/SLL, warranting continued clinical investigation.