bluuebunny/crossref_metadata_2025 huggingface dataset:
Vernacular journalism: Local news and everyday life
Authors: Wahl-Jorgensen Karin , Boelle Julia
Published: October 2023

This paper, based on in-depth interviews with 57 local journalism entrepreneurs in the UK, develops the idea that these emergent and small-scale local news organizations prioritize a form of “vernacular journalism.” Driven by a democratic impulse, vernacular journalism reflects the preoccupations, experiences and histories of ordinary people and their communities, providing a vehicle for representation and voice, which is often missing from more established news organizations. Vernacular journalism seeks to (1) make a difference in the local community, and (2) represent the nature of the community, providing a “first draft” of its history from its inhabitants’ perspective. The ability to provide such vernacular journalism is premised on knowledge of the community, cultivated through long-standing presence. The provision of a vernacular journalism which reflects the world from the bottom up is a unique selling point for local journalism, against the top-down orientation of larger regional and national outlets.
The lab, land, and longing: Discursive constructions of Australian identities in ‘future’ food consumption
Authors: Errmann Amy , Conroy Denise M. , Young Jennifer
Published: October 2023

Food consumption is being reconfigured as a consequence of consumers’ ethical concerns. While preferences and tastes may be influenced by broad ethical positions, constructions of social identity also reflect shifts in food consumption. Important tools within this nexus are ‘future foods’, produced through novel technologies such as artificial intelligence or genetic editing, supporting consumers in the construction of identity markers. Through 24 ( n = 121) focus groups in rural and urban Australia, we explore to what extent future foods contribute to alleviate tensions between broader ethical principles and consumer identities. We argue that the collective discourse around future foods has the potential to shift the culture of food ethics in the future, enabled through three moral identity markers. Specifically, identities of citizen-consumption that view ethics as ‘eating for change’; nationalism as a form of patriotic morality that encourages the consumption of national brands and protectionism; and nostalgic knowledge and historical identities of the past to reconfigure ethical ideals for the future. These discursive identity constructions shed light on how consumers may redefine food ethics in the future, legitimising citizenship through demonstrating virtue, patriotism as loyalty to social groups, and nostalgic capturing of history to ‘ethicise’ the future.
Robust function-on-function interaction regression
Authors: Beyaztas Ufuk , Shang Han Lin , Mandal Abhijit
Published: October 2023

A function-on-function regression model with quadratic and interaction effects of the covariates provides a more flexible model. Despite several attempts to estimate the model’s parameters, almost all existing estimation strategies are non-robust against outliers. Outliers in the quadratic and interaction effects may deteriorate the model structure more severely than their effects in the main effect. We propose a robust estimation strategy based on the robust functional principal component decomposition of the function-valued variables and [Formula: see text]-estimator. The performance of the proposed method relies on the truncation parameters in the robust functional principal component decomposition of the function-valued variables. A robust Bayesian information criterion is used to determine the optimum truncation constants. A forward stepwise variable selection procedure is employed to determine relevant main, quadratic, and interaction effects to address a possible model misspecification. The finite-sample performance of the proposed method is investigated via a series of Monte-Carlo experiments. The proposed method’s asymptotic consistency and influence function are also studied in the supplement, and its empirical performance is further investigated using a U.S. COVID-19 dataset.
“We are not labors; we are teachers”: Indonesian early childhood teachers’ organizations as a form of a panopticon
Authors: Yulindrasari Hani , Adriany Vina
Published: October 2023

This paper aims to unpack the discourses of teachers’ professionalism and teachers’ organizations in the early childhood education settings in Indonesia. Using Foucault's notions of discourse and power, we are interested in exploring how both discourses have silenced the teachers. This paper adopts qualitative research conducted with nine teachers, all active members, and boards of ECE teachers’ organizations. The data were collected mainly through semi-formal interviews and focus group discussions. The data were analyzed using a thematic approach. The findings suggest how the teachers’ organization has acted as a form of panopticon that sustains the hegemonic definition of teachers’ professionalism. The findings also suggest that the teachers’ understanding of professionalism is also highly influenced by the local/Javanese values of halus, where teaching is seen as a noble and refined profession. Hence, teachers continue to create the binary between teaching and working. At the same time, the penetration of religious discourse has also situated them to accept their situation. This paper, therefore, serves as an invitation to rethink and reimagine the kind of policies and educational reform needed so that the teachers can have a space to voice their struggle.
Epidemiology and geographic clustering of Erdheim-Chester disease in Italy and France
Authors: Peyronel Francesco , Haroche Julien , Campochiaro Corrado , Pegoraro Francesco , Amoura Zahir , Tomelleri Alessandro , Mazzariol Martina , Papo Matthias , Cavalli Giulio , Benigno Giuseppe D. , Fenaroli Paride , Grigoratos Chrysanthos , Mengoli Maria C. , Bonometti Arturo , Berti Emilio , Savino Gustavo , Cives Mauro , Neri Iria , Pacinella Gaetano , Tuttolomondo Antonino , Marano Massimo , Muratore Francesco , Manfredi Andreina , Broccoli Alessandro , Zinzani Pier L. , Didona Biagio , Massaccesi Chiara , Buono Andrea , Ammirati Enrico , Di Lernia Vito , Dagna Lorenzo , Vaglio Augusto , Cohen-Aubart Fleur
Published: October 2023

This geoepidemiological study, performed in Italy and France, shows that Erdheim-Chester disease is increasingly diagnosed and cases cluster in specific geographic areas, namely southern Italy and central France. Disease frequency inversely correlates with the Human Development Index.
Response-adapted, time-limited venetoclax, umbralisib, and ublituximab for relapsed/refractory chronic lymphocytic leukemia
Authors: Hill Brian T. , Ma Shuo , Zent Clive S. , Baran Andrea M. , Wallace Danielle S. , Advani Anjali , Winter Allison , Winter Jane , Gordan Leo , Karmali Reem , Liesveld Jane L. , Mulford Deborah A. , Rowland Chris , Bui Andrew , Sportelli Peter , Miskin Hari P. , Weiss Michael S. , Friedberg Jonathan W. , Barr Paul M.
Published: October 2023

Many patients with chronic lymphocytic leukemia (CLL) will develop treatment resistance to Bruton tyrosine kinase (BTK) inhibitors. Phosphatidylinositol-3-kinase (PI3K) inhibitors, including umbralisib, have significant clinical activity in relapsed/refractory CLL, but prolonged exposure is associated with potential toxicities. Owing to the synergistic antitumor effects of combined PI3K and BCL-2 inhibition, we sought to explore the feasibility of response-adapted, time-limited therapy to optimize disease control while mitigating the risks of prolonged treatment. We conducted a phase 1/2 clinical trial to determine the safety and efficacy of venetoclax in combination with umbralisib and the anti-CD20 monoclonal antibody, ublituximab, (U2-VeN) in patients with relapsed/refractory CLL (N = 46) and Richter transformation (N = 5). After 12 cycles, treatment was stopped for patients with CLL who achieved undetectable minimal residual disease (uMRD). Adverse events of special interest included diarrhea in 50% of patients (11% grade 3/4), and aspartate aminotransferase and/or alanine aminotransferase elevation in 15 patients (33%), with 3 (7%) grade 3/4. There were no cases of tumor lysis syndrome related to venetoclax, with outpatient initiation in 96% of patients. The intent-to-treat overall response rate for CLL was 98% with best response of 100% in evaluable patients (42% complete responses). The end-of-treatment rate of uMRD at 10−4 in bone marrow was 77% (30/39), including a 71% uMRD rate among 14 patients refractory to prior BTK inhibitor. Time-limited venetoclax and U2 is safe and highly effective combination therapy for patients with relapsed/refractory CLL including those who have been previously treated with covalent BTK inhibitors. This trial was registered on www.clinicaltrials.gov as #NCT03379051.
A CD3 humanized mouse model unmasked unique features of T-cell responses to bispecific antibody treatment
Authors: Wang Lingling , Leach Vincent , Muthusamy Natarajan , Byrd John , Long Meixiao
Published: October 2023

T-cell bispecific antibodies (T-BsAbs) such as blinatumomab hold great promise for cancer immunotherapy. A better understanding of the in vivo immune response induced by T-BsAbs is crucial to improving their efficacy and safety profile. However, such efforts are hindered by the limitations of current preclinical models. To address this, we developed a syngeneic murine model with humanized CD3 and target antigen (CD20). This model enables the development of disseminated leukemia with a high tumor burden, which mirrors clinical findings in human patients with relapsed/refractory acute lymphoblastic leukemia. Treatment of this model with T-BsAbs results in cytokine release syndrome, with cytokine profiles and levels reflecting observations made in human patients. This model also faithfully recapitulates the dynamics of T-cell activation seen in human patients, including the temporary disappearance of T cells from the bloodstream. During this phase, T cells are sequestered in secondary lymphoid organs and undergo activation. Clinical correlative studies that rely primarily on peripheral blood samples are likely to overlook this critical activation stage, leading to a substantial underestimation of the extent of T-cell activation. Furthermore, we demonstrate that surface expression of the T-BsAb target antigen by leukemia cells triggers a swift immune response, promoting their own rejection. Humanizing the target antigen in the recipient mice is crucial to facilitate tolerance induction and successful establishment of high tumor burden. Our findings underscore the importance of meticulously optimized syngeneic murine models for investigating T-BsAb–induced immune responses and for translational research aimed at improving efficacy and safety.
Blinatumomab consolidation post–autologous stem cell transplantation in patients with diffuse large B-cell lymphoma
Authors: Ghobadi Armin , Foley Nicole C. , Cohen Jared , Rettig Michael P. , Cashen Amanda F. , Gehrs Leah , Christ Stephanie , Street Emily , Wallace Nicholas , Ritchey Julie , Mehta-Shah Neha , Westervelt Peter , Fehniger Todd A. , Kahl Brad , Bartlett Nancy L. , DiPersio John F.
Published: October 2023

Outcomes in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who undergo autologous stem cell transplant (auto-SCT) are poor. Blinatumomab is a CD3/CD19 bispecific T-cell engager that directs cytotoxic T cells to CD19+ cells. Here, we performed a pilot study of blinatumomab consolidation after auto-SCT for 14 patients with DLBCL or transformed follicular lymphoma. All patients underwent standard-of-care auto-SCT with carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning followed by 1 cycle (4 weeks continuous infusion) of blinatumomab consolidation starting at day 42 after auto-SCT. All 14 patients treated on study completed BEAM auto-SCT and 1 cycle of posttransplant blinatumomab. Five patients developed grade 1 cytokine release syndrome (CRS), with no grade 2 or higher CRS. Immune effector cell–associated neurotoxicity syndrome was not observed. Patients were followed up for 3 years after auto-SCT, with median follow-up of 37 (range, 12-65) months. One-hundred days after auto-SCT (1 month after blinatumomab consolidation), 12 patients (86%) had achieved complete remission. At 1 year after auto-SCT, 7 patients (50%) remained in CR, and 1 patient had died of progressive disease. Patients who relapsed had a lower CD8:CD4 T-cell ratio before starting blinatumomab than patients who remained in remission. This pilot study demonstrates blinatumomab consolidation after auto-SCT is safe and well tolerated. Strategies to increase the CD8:CD4 ratio and use additional cycles of consolidation in a larger randomized trial are needed to confirm the efficacy of consolidation with blinatumomab after auto-SCT. This trial was registered at www.clinicaltrials.gov as #NCT03072771.
High PDL1/PDL2 gene expression correlates with worse outcome in primary mediastinal large B-cell lymphoma
Authors: Camus Vincent , Viailly Pierre-Julien , Drieux Fanny , Veresezan Elena-Liana , Sesques Pierre , Haioun Corinne , Durot Eric , Patey Martine , Rossi Cédric , Martin Laurent , Rainville Vinciane , Bohers Elodie , Ruminy Philippe , Penther Dominique , Kaltenbach Sophie , Bruneau Julie , Paillassa Jérome , Tournilhac Olivier , Willaume Alexandre , Antier Chloé , Lazarovici Julien , Lévêque Emilie , Decazes Pierre , Becker Stéphanie , Tonnelet David , Berriolo-Riedinger Alina , Gaulard Philippe , Tilly Hervé , Molina Thierry Jo , Traverse-Glehen Alexandra , Jardin Fabrice
Published: October 2023

Primary mediastinal B-cell lymphoma (PMBL) is an uncommon entity of aggressive B-cell lymphoma with an unusually good prognosis, except for 10-15% of chemotherapy-refractory cases. To identify earlier these higher risk patients, we performed molecular characterization of a retrospective multicenter cohort of patients treated with firstline immunochemotherapy. The traits of the patients with gene-expression profiling data (n = 120) were as follows: median age of 34 years (range, 18-67 years); female sex, 58.3%; elevated lactate dehydrogenase, 82.5%; Eastern Cooperative Oncology Group performance status score of 0 to 1, 85.7%; Ann Arbor stage I/II, 55%; International Prognostic Index score of 1 to 2, 64.4%; and median metabolic tumor volume, 290.4 cm3 (range, 15.7-1147.5 cm3). Among all 137 markers tested for correlation with survival data, only programmed death-ligand (PDL) 1 and PDL2 expression showed a prognostic impact. Overall, both PDL1 and PDL2 genes were highly expressed in 37 patients (30.8%; PDL1high/PDL2high). The baseline clinical characteristics of patients with PDL1high/PDL2high were similar to those of other patients. In univariate analysis, PDL1high/PDL2high status was associated with poor progression-free survival (PFS) (hazard ratio [HR], 4.292) and overall survival (OS; HR, 8.24). In multivariate analysis, PDL1high/PDL2high status was an independent prognostic factor of adverse outcomes (PFS: HR, 5.22; OS: HR, 10.368). We validated these results in an independent cohort of 40 patients and confirmed the significant association between PDL1high/PDL2high status and inferior PFS (HR, 6.11). High PDL1/PDL2 gene expression defines a population with strong immune privilege and poorer outcomes from standard chemotherapy who might benefit from firstline checkpoint inhibitor therapy.
Vision Sensing-Based Online Correction System for Robotic Weld Grinding
Authors: Ge Jimin , Deng Zhaohui , Wang Shuixian , Li Zhongyang , Liu Wei , Nie Jiaxu
Published: October 2023

The service cycle and dynamic performance of structural parts are affected by the weld grinding accuracy and surface consistency. Because of reasons such as assembly errors and thermal deformation, the actual track of the robot does not coincide with the theoretical track when the weld is ground offline, resulting in poor workpiece surface quality. Considering these problems, in this study, a vision sensing-based online correction system for robotic weld grinding was developed. The system mainly included three subsystems: weld feature extraction, grinding, and robot real-time control. The grinding equipment was first set as a substation for the robot using the WorkVisual software. The input/output (I/O) ports for communication between the robot and the grinding equipment were configured via the I/O mapping function to enable the robot to control the grinding equipment (start, stop, and speed control). Subsequently, the Ethernet KRL software package was used to write the data interaction structure to realize real-time communication between the robot and the laser vision system. To correct the measurement error caused by the bending deformation of the workpiece, we established a surface profile model of the base material in the weld area using a polynomial fitting algorithm to compensate for the measurement data. The corrected extracted weld width and height errors were reduced by 2.01% and 9.3%, respectively. Online weld seam extraction and correction experiments verified the effectiveness of the system’s correction function, and the system could control the grinding trajectory error within 0.2 mm. The reliability of the system was verified through actual weld grinding experiments. The roughness, Ra, could reach 0.504 µm and the average residual height was within 0.21 mm. In this study, we developed a vision sensing-based online correction system for robotic weld grinding with a good correction effect and high robustness.
CRISPR/Cas9-based depletion of 16S ribosomal RNA improves library complexity of single-cell RNA-sequencing in planarians
Authors: Wang Kuang-Tse , Adler Carolyn E.
Published: October 2023

Background

Single-cell RNA-sequencing (scRNA-seq) relies on PCR amplification to retrieve information from vanishingly small amounts of starting material. To selectively enrich mRNA from abundant non-polyadenylated transcripts, poly(A) selection is a key step during library preparation. However, some transcripts, such as mitochondrial genes, can escape this elimination and overwhelm libraries. Often, these transcripts are removed in silico, but whether physical depletion improves detection of rare transcripts in single cells is unclear.

Results

We find that a single 16S ribosomal RNA is widely enriched in planarian scRNA-seq datasets, independent of the library preparation method. To deplete this transcript from scRNA-seq libraries, we design 30 single-guide RNAs spanning its length. To evaluate the effects of depletion, we perform a side-by-side comparison of the effects of eliminating the 16S transcript and find a substantial increase in the number of genes detected per cell, coupled with virtually complete loss of the 16S RNA. Moreover, we systematically determine that library complexity increases with a limited number of PCR cycles following CRISPR treatment. When compared to in silico depletion of 16S, physically removing it reduces dropout rates, retrieves more clusters, and reveals more differentially expressed genes.

Conclusions

Our results show that abundant transcripts reduce the retrieval of informative transcripts in scRNA-seq and distort the analysis. Physical removal of these contaminants enables the detection of rare transcripts at lower sequencing depth, and also outperforms in silico depletion. Importantly, this method can be easily customized to deplete any abundant transcript from scRNA-seq libraries.
Genome-wide allele frequency studies in Pacific oyster families identify candidate genes for tolerance to ostreid herpesvirus 1 (OsHV-1)
Authors: Divilov Konstantin , Merz Noah , Schoolfield Blaine , Green Timothy J. , Langdon Chris
Published: October 2023

Background

Host genetics influences the development of infectious diseases in many agricultural animal species. Identifying genes associated with disease development has the potential to make selective breeding for disease tolerance more likely to succeed through the selection of different genes in diverse signaling pathways. In this study, four families of Pacific oysters (Crassostrea gigas) were identified to be segregating for a quantitative trait locus (QTL) on chromosome 8. This QTL was previously found to be associated with basal antiviral gene expression and survival to ostreid herpesvirus 1 (OsHV-1) mortality events in Tomales Bay, California. Individuals from these four families were phenotyped and genotyped in an attempt to find candidate genes associated with the QTL on chromosome 8.

Results

Genome-wide allele frequencies of oysters from each family prior to being planting in Tomales Bay were compared with the allele frequencies of oysters from respective families that survived an OsHV-1 mortality event. Six significant unique QTL were identified in two families in these genome-wide allele frequency studies, all of which were located on chromosome 8. Three QTL were assigned to candidate genes (ABCA1,PIK3R1, andWBP2) that have been previously associated with antiviral innate immunity in vertebrates.

Conclusion

The identification of vertebrate antiviral innate immunity genes as candidate genes involved in molluscan antiviral innate immunity reinforces the similarities between the innate immune systems of these two groups. Causal variant identification in these candidate genes will enable future functional studies of these genes in an effort to better understand their antiviral modes of action.
Establishing the core elements of a frailty at the front door model of care using a modified real-time Delphi technique
Authors: O’Shaughnessy Íde , Fitzgerald Christine , Whiston Aoife , Harnett Patrick , Whitty Helen , Mulligan Des , Mullaney Marian , Devaney Catherine , Lang Deirdre , Hardimann Jennifer , Condon Brian , Hayes Christina , Holmes Alison , Barry Louise , McCormack Claire , Bounds Megan , Robinson Katie , O’Connor Margaret , Ryan Damien , Shchetkovsky Denys , Steed Fiona , Carey Leonora , Ahern Emer , Galvin Rose
Published: October 2023

Background

Innovations in models of care for older adults living with frailty presenting to the emergency department (ED) have become a key priority for clinicians, researchers and policymakers due to the deleterious outcomes older adults experience due to prolonged exposure to such an environment. This study aimed to develop a set of expert consensus-based statements underpinning operational design, outcome measurement and evaluation of a Frailty at the Front Door (FFD) model of care for older adults within an Irish context.

Methods

A modified real-time Delphi method was used. Facilitation of World Café focus groups with an expert panel of 86 members and seperate advisory groups with a Public and Patient Involvement panel of older adults and members of the Irish Association of Emergency Medicine generated a series of statements on the core elements of the FFD model of care. Statements were analysed thematically and incorporated into a real-time Delphi survey, which was emailed to members of the expert panel. Members were asked to rank 70 statements across nine domains using a 9-point Likert scale. Consensus criteria were defined a priori and guided by previous research using 9-point rating scales.

Results

Fifty members responded to the survey representing an overall response rate of 58%. Following analyses of the survey responses, the research team reviewed statements for content overlap and refined a final list of statements across the following domains: aims and objectives of the FFD model of care; target population; screening and assessment; interventions; technology; integration of care; evaluation and metrics; and research.

Conclusion

Development of a consensus derived FFD model of care represents an important step in generating national standards, implementation of a service model as intended and enhances opportunities for scientific impact. Future research should focus on the development of a core outcome set for studies involving older adults in the ED.
Severe anemia, severe leukopenia, and severe thrombocytopenia of amphotericin B deoxycholate-based induction therapy in patients with HIV-associated talaromycosis: a subgroup analysis of a prospective multicenter cohort study
Authors: Zhou Yihong , Lu Tao , Li Yan , Qin Yuanyuan , Lu Yanqiu , Tian Qun , Lan Ke , Zhou Guoqiang , Qin Yingmei , Harypursat Vijay , Li Shunmei , Lin Shide , Chen Yaokai
Published: October 2023

Background

This study’s objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV-infected patients with talaromycosis.

Methods

A total of 170 HIV-infected patients with talaromycosis were enrolled from January 1st, 2019, to September 30th, 2020.

Results

Approximately 42.9%, 20.6%, and 10.6% of the enrolled patients developed severe anemia, severe leukopenia, and severe thrombocytopenia, respectively. Baseline hemoglobin level < 100 g/L (OR = 5.846, 95% CI: 2.765 ~ 12.363), serum creatinine level > 73.4 µmol/L (OR = 2.573, 95% CI: 1.157 ~ 5.723), AST/ALT ratio > 1.6 (OR = 2.479, 95% CI: 1.167 ~ 5.266), sodium level ≤ 136 mmol/liter (OR = 4.342, 95% CI: 1.747 ~ 10.789), and a dose of amphotericin B deoxycholate > 0.58 mg/kg/d (OR = 2.504, 95% CI:1.066 ~ 5.882) were observed to be independent risk factors associated with the development of severe anemia. Co-infection with tuberculosis (OR = 3.307, 95% CI: 1.050 ~ 10.420), and platelet level (per 10 × 109 /L) (OR = 0.952, 95% CI: 0.911 ~ 0.996) were shown to be independent risk factors associated with the development of severe leukopenia. Platelet level < 100 × 109 /L (OR = 2.935, 95% CI: 1.075 ~ 8.016) was identified as the independent risk factor associated with the development of severe thrombocytopenia. There was no difference in progression to severe anemia, severe leukopenia, and severe thrombocytopenia between the patients with or without fungal clearance at 2 weeks. 10 mg on the first day of amphotericin B deoxycholate was calculated to be independent risk factors associated with the development of severe anemia (OR = 2.621, 95% CI: 1.107 ~ 6.206). The group receiving a starting amphotericin B dose (10 mg, 20 mg, daily) exhibited the highest fungal clearance rate at 96.3%, which was significantly better than the group receiving a starting amphotericin B dose (5 mg, 10 mg, 20 mg, daily) (60.9%) and the group receiving a starting amphotericin B dose (5 mg, 15 mg, and 25 mg, daily) (62.9%).

Conclusion

The preceding findings reveal risk factors for severe anemia, severe leukopenia, and severe thrombocytopenia. After treatment with Amphotericin B, these severe adverse events are likely unrelated to fungal clearance at 2 weeks. Starting amphotericin B deoxycholate at a dose of 10 mg on the first day may increase the risk of severe anemia but can lead to earlier fungal clearance.

Trial registration

ChiCTR1900021195. Registered 1 February 2019.
Awareness of and willingness to use oral pre-exposure prophylaxis (PrEP) for HIV prevention among sexually active adults in Malawi: results from the 2020 Malawi population-based HIV impact assessment
Authors: Kabaghe Alinune Nathanael , Singano Victor , Payne Danielle , Maida Alice , Nyirenda Rose , Mirkovic Kelsey , Jahn Andreas , Patel Pragna , Brown Kristin , Farahani Mansoor , Kayigamba Felix , Tenthani Lyson , Ogollah Francis , Auld Andrew , Zulu Fatima , Msungama Wezi , Wadonda-Kabondo Nellie
Published: October 2023

Background

The World Health Organization recommends Pre-Exposure Prophylaxis (PrEP) for all populations at substantial risk of HIV infection. Understanding PrEP awareness and interest is crucial for designing PrEP programs; however, data are lacking in sub-Saharan Africa. In Malawi, oral PrEP was introduced in 2018. We analyzed data from the 2020 Malawi Population-based HIV Impact Assessment (MPHIA) to assess PrEP awareness and factors associated with PrEP interest in Malawi.

Methods

MPHIA 2020 was a national cross-sectional household-based survey targeting adults aged 15 + years. Oral PrEP was first described to the survey participants as taking a daily pill to reduce the chance of getting HIV. To assess awareness, participants were asked if they had ever heard of PrEP and to assess interest, were asked if they would take PrEP to prevent HIV, regardless of previous PrEP knowledge. Only sexually active HIV-negative participants are included in this analysis. We used multivariable logistic regression to assess sociodemographic factors and behaviors associated with PrEP interest. All results were weighted.

Results

We included 13,995 HIV-negative sexually active participants; median age was 29 years old. Overall, 15.0%, 95% confidence interval (CI): 14.2–15.9% of participants were aware of PrEP. More males (adjusted odds ratio (aOR): 1.3, 95% CI: 1.2–1.5), those with secondary (aOR: 1.5, 95% CI: 1.2-2.0) or post-secondary (aOR: 3.4, 95% CI: 2.4–4.9) education and the wealthiest (aOR: 1.6, 95% CI: 1.2-2.0) were aware of PrEP than female, those without education and least wealthy participants, respectively. Overall, 73.0% (95% CI: 71.8–74.1%) of participants were willing to use PrEP. Being male (aOR: 1.2; 95% CI: 1.1–1.3) and having more than one sexual partner (aOR: 1.7 95% CI: 1.4–1.9), were associated higher willingness to use PrEP.

Conclusions

In this survey, prior PrEP knowledge and use were low while PrEP interest was high. High risk sexual behavior was associated with willingness to use PrEP. Strategies to increase PrEP awareness and universal access, may reduce HIV transmission.
Ceftazidime/avibactam combined with colistin: a novel attempt to treat carbapenem-resistant Gram-negative bacilli infection
Authors: Zheng Zihao , Shao Ziqiang , Lu Lihai , Tang Siyu , Shi Kai , Gong Fangxiao , Liu Jingquan
Published: October 2023

Background

The rapid global emergence and spread of carbapenem-resistant Gram-negative bacilli (CR-GNB) is recognized as a major public health concern, and there are currently few effective treatments for CR-GNB infection. The aim of this study was to investigate the clinical characteristics and outcomes of patients with CR-GNB infections treated with ceftazidime/avibactam (CAZ/AVI) combined with colistin from October 2019 to February 2023 in China.

Methods

A total of 31 patients with CR-GNB infections were retrospectively identified using the electronic medical record system of Zhejiang Provincial People's Hospital.

Results

Thirty-one patients were treated with CAZ/AVI combined with colistin. Respiratory tract infections (87%) were most common. The common drug-resistant bacteria encompass Klebsiella pneumonia (54.8%), Acinetobacter baumannii (29.0%), and Pseudomonas aeruginosa (16.1%). The 30-day mortality rate was 29.0%, and the 7-day microbial clearance rate was 64.5%. The inflammatory marker CRP changes, but not PCT and WBC, were statistically significant on days 7 and 14 after combination therapy. There were seven patients developing acute renal injury (AKI) after combination therapy and treating with continuous renal replacement therapy (CRRT). Two patients developed diarrhea.

Conclusion

The combination of CAZ/AVI and colistin has potential efficacy in patients with CR-GNB infection, but more studies are needed to determine whether it can reduce 30-day mortality rates and increase 7-day microbial clearance. At the same time, the adverse reactions of combination therapy should not be ignored.
Percutaneous radiofrequency thermocoagulation and microvascular decompression for treating glossopharyngeal neuralgia: a retrospective clinical study
Authors: Wu Zeyu , Zhao Yongming , Wu Fan , Fan Yiyue , Yang Ying
Published: October 2023

Objectives

This study aimed to investigate the differences in the effectiveness of percutaneous radiofrequency thermocoagulation (PRT) and microvascular decompression (MVD) in treating glossopharyngeal neuralgia (GPN).

Methods

Medical records of patients were reviewed to investigate their baseline characteristics and immediate postoperative prognosis. Long-term outcomes of these patients were obtained through telephone interviews. Visual analog scale (VAS) and Pittsburgh sleep quality index (PSQI) scores at 1 day and 1, 4, 12, 24, and 48 weeks after surgery were compared between the MVD and PRT groups, in addition to complete pain relief rate, effective rate, adverse reactions, length of hospital stay, and economic indicators.

Results

The VAS and PSQI scores of the two groups at 1 day and 1, 4, 12, 24, and 48 weeks after surgery were significantly lower (P < 0.05) than those before surgery. At 48 weeks, the complete remission rate was significantly higher (P < 0.05) in the MVD group than in PRT group. No significant difference in adverse reactions was observed between the two groups. The length of hospital stay, operative time, and cost were significantly higher (P < 0.05) in the MVD group than in the PRT group.

Conclusions

Both PRT and MVD can significantly reduce patients’ degree of pain and improve their sleep quality. In the medium term, MVD is better than PRT in terms of the complete curative effect. In young patients with GPN, MVD is more often recommended than PRT; however, MVD is costlier than PRT.
Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro
Authors: Li Yanze , Xu Kai , Zhang Ye , Mao Hu , Qiu Qiangmin , Yan Zhiwei , Liu Xiuheng , Du Yang , Chen Zhiyuan
Published: October 2023

Background

Bladder urothelial carcinoma (BLCA) is the most common genitourinary cancer and the prognosis of patients is often poor. However, studies of basement membrane-related genes (BM-related genes) in BLCA are less reported. Therefore, we established a BM-related genes signature to explore their functional and prognostic value in BLCA.

Methods

In this study, a BM-related genes signature was constructed by LASSO-Cox regression analysis, and then a series of bioinformatics methods was used to assess the accuracy and validity of the signature. We constructed a nomogram for clinical application and also screened for possible therapeutic drugs. To investigate the functions and pathways affected by BM-related genes in BLCA, we performed functional enrichment analyses. In addition, we analyzed the immune cell infiltration landscape and immune checkpoint-related genes in the high and low-risk groups. Finally, we confirmed the prognostic value of BM-related genes in BLCA in vitro.

Results

Combining multiple bioinformatics approaches, we identified a seven-gene signature. The accuracy and validity of this signature in predicting BLCA patients were confirmed by the test cohort. In addition, the risk score was strongly correlated with prognosis, immune checkpoint genes, drug sensitivity, and immune cell infiltration landscape. The risk score is an independent prognostic factor for BLCA patients. Further experiments revealed that all seven signature genes were differentially expressed between BLCA cell lines and normal bladder cells. Finally, overexpression of LAMA2 inhibited the migration and invasion ability of BLCA cell lines.

Conclusions

In summary, the BM-related genes signature was able to predict the prognosis of BLCA patients accurately, indicating that the BM-related genes possess great clinical value in the diagnosis and treatment of BLCA. Moreover, LAMA2 could be a potential therapeutic target, which provides new insights into the application of the BM-related genes in BLCA patients.
Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients
Authors: Zhou Yuxin , Mu Wenjing , Wang Chen , Zhuo Zipeng , Xin Yu , Li Hongxu , Wang Changsong
Published: October 2023

Background

Chimeric antigen receptor T (CAR-T) cell therapy, a new adoptive cell therapy, has been widely used to treat lymphoma patients. Immune checkpoint blockade may improve the cytotoxicity of CAR-T cells by reducing the failure of CAR-T cells and improving antitumor activity. It has shown promising efficacy.

Method

We searched PubMed, the Cochrane Library, Embase and Web of Science from January 2012 to August 2022 to find data reporting the results of CAR-T cells therapy combined with PD-1 in tumor patients. An updated search was conducted in October 2023. The partial response rate (PR), complete response rate (CR), objective response rate (ORR), mortality rate, and incidence of adverse reactions were calculated.

Results

We analyzed 57 lymphoma patients from 5 clinical trials. The pooled partial, complete and overall response rates were 21% (95% CI 0.06–0.39, I2 = 0.37%), 27% (95% CI 0.03–0.60, I2 = 60.43%) and 65% (95% CI 0.23–0.98, I2 = 76.31%), respectively. The pooled incidence of cytokine release syndrome, neutropenia, fever, and fatigue was estimated to be 57% (95% CI 0.08–0.99, I2 = 85.20%), 47% (95% CI 0.14–0.81, I2 = 74.17%), 59% (95% CI 0.27–0.89, I2 = 60.23%), and 50% (95% CI 0.13–0.87, I2 = 73.89%), respectively.

Conclusion

CAR-T-cell therapy combined with anti-PD-1 immunotherapy in the treatment of lymphoma patients has efficacy, and the most common adverse effect is fever.

Registration

The protocol was registered in prospero, with the registration number CRD42022342647.
Analysis of hindering and facilitating factors of help-seeking behavior in schizophrenia based on COM-B model: a descriptive qualitative study
Authors: Ma Rui , Wang Yu , Wang Xiao-qing , Yu Kai , Zhang Chen-chen , Zhou Yu-qiu
Published: October 2023

Background

Timely and systematic professional treatment is crucial in schizophrenia prognosis, but the global rate of mental health service, now, use or help-seeking behavior is low.

Methods

In-depth semi-structured interviews were conducted with 13 participants with the diagnosis of schizophrenia between October to December 2021. The participants were purposively sampled from a psychiatric hospital’s. Interviews were recorded and transcribed verbatim into NVivo 12.0.

Results

The findings were summarized under 3 themes and 12 subthemes: (1) capability (lack of knowledge due to insufficient mental health literacy or lack of insight, inability to access disease information due to a lack of mental health literacy, and symptoms-related barriers); (2) opportunity (lack of disease information sources, inability to balance work and study during prolonged hospitalization, accessibility and convenience of medical resources, and the acquisition and utilization of social support); and (3) motivation (awareness of the disease and professional treatment, negative experiences of disease episodes, past medical experience, confidence in tcuring the disease, and the fulfillment of daily life and self-worth).

Conclusion

The medical help-seeking behavior of people with the diagnosis of schizophrenia is the result of the interaction of many barriers and facilitators, and challenges persist today. Interventions can be implemented with the BCW framework and our results to precisely eliminate delays in the diagnosis and treatment of mental problems.
Youth experiences with and perspectives on long covid
Authors: Irani Sarosh , Chang Claire , Morrison Leigh , Waselewski Marika , Chang Tammy
Published: October 2023

Background

Research on the long-term effects of COVID-19 infection is ongoing, and the psychological and physical impacts of Long Covid on youth is poorly understood. To assess these impacts, we surveyed youth regarding their experiences with, and perspectives on, the long-term effects of COVID-19.

Methods

We conducted a nationwide text message survey of youth ages 14–24 years in the United States. The survey asked four open ended questions regarding their experiences and perceptions regarding the long-term effects of COVID-19. Qualitative data was analyzed independently by three investigators using thematic analysis. Prevalence of codes were summarized using descriptive statistics.

Results

Among 1150 participants, 991 responded to at least one survey question (response rate 86.1%). The vast majority of our sample had COVID-19 or knew someone who did (75%), and approximately one third (32%) of youth indicated that they knew someone who had experienced symptoms consistent with Long Covid. Many youth (50%) reported worry and concern about Long Covid even if they, or someone they knew, did not have Long Covid. Among youth who were not concerned about Long Covid, the most commonly reported reasons were having received the vaccine (29%) and not having a prior COVID-19 infection (24%).

Conclusions

Our findings suggest that among younger populations, there is significant concern regarding the long-term effects of COVID-19. Vaccination campaigns and youth-centered public health communication about Long Covid may not only reduce COVID-19 transmission, but also alleviate worries and concerns about Long Covid among youth.
The association of the quality of life with Afghan households’ food insecurity before and after the recent political change in Afghanistan: a comparative analysis
Authors: Saif-Nijat Jumakhan , Pakravan-Charvadeh Mohammad Reza , Gholamrezai Saeed , Rahimian Mehdi , Lane Ginny , Béland Daniel , Koc Mustafa , Clark Nancy , Omidvar Nasrin , Sadeghi Rasoul , Vatanparast Hassan
Published: October 2023

The overreaching objective of the current study is to investigate the association of quality of life with Afghan households’ food insecurity. The data was collected immediately after the Taliban took control of a large part of Afghanistan. About a total of 555 households’ heads participated in a face-to-face interview, using the HFIAS and WHOQOL-100 questionnaires along with some questions related to their socioeconomic characteristics at two different times, before and after the Taliban’s takeover. The comparative analysis showed that 98% of Afghan households were food insecure after the Taliban takeover, while 70% of them faced food insecurity before the Taliban’s takeover. The quality of life in the Taliban era is worse than before the Taliban. All dimensions of quality of life have decreased, and this decrease was more pronounced for the psychological, environmental, and physical domains. It is recommended that international organizations, NGOs, and local agents focus on these dimensions of the quality of life to improve food security.
Knowledge, safety, and impact of alcohol consumption in young adults with type 1 diabetes mellitus: a qualitative study
Authors: Sergel-Stringer Oscar T , Al-Sallami Hesham S , Styles Sara E , Boucsein Alisa , de Bock Martin I , Wheeler Benjamin J
Published: October 2023

Purpose

To explore the lived experiences of alcohol consumption among young adults with type 1 diabetes.

Methods

Fourteen semi-structured interviews were conducted amongst young adults aged between 18 and 25 years, inclusive, with type 1 diabetes and experience consuming alcohol. Interviews were transcribed verbatim and analysed to identify common themes regarding their experiences.

Results

The interviews confirmed that young adults with type 1 diabetes engage in social, and occasionally excessive, drinking behaviour. Furthermore, the interviews revealed four key themes: (i) Several sources contribute to a widely inconsistent understanding of the impact and management of alcohol consumption; (ii) Perceived inconvenience of maintaining healthy glycaemic control whilst drinking socially; (iii) Engagement in proactive strategies for harm reduction occurred when convenient; and (iv) Impact of modern diabetes technology in overcoming previous burdens and promoting glycaemic safety.

Conclusion

Young adults with type 1 diabetes continue to need anticipatory education surrounding safe alcohol consumption and behaviours, as well as ongoing support and encouragement to ensure engagement with traditional self-management tasks. Significant alcohol-diabetes related safety issues, particularly hypoglycaemia do occur, and were captured within this small sample and study. Diabetes technology has an important complementary role along with education and tailored support strategies to support health and safe glucose control during alcohol consumption.
Tomo-seq identifies NINJ1 as a potential target for anti-inflammatory strategy in thoracic aortic dissection
Authors: Sheng Yixuan , Wu Liying , Chang Yuan , Liu Wendao , Tao Menghao , Chen Xiao , Zhang Xiong , Li Bin , Zhang Ningning , Ye Dongting , Zhang Chunxi , Zhu Daliang , Zhao Haisen , Chen Aijun , Chen Haisheng , Song Jiangping
Published: October 2023

Background

Thoracic aortic dissection (TAD) is a life-threatening disease caused by an intimal tear in the aorta. The histological characteristics differ significantly between the tear area (TA) and the distant area. Previous studies have emphasized that certain specific genes tend to cluster at the TA. Obtaining a thorough understanding of the precise molecular signatures near the TA will assist in discovering therapeutic strategies for TAD.

Methods

We performed a paired comparison of the pathological patterns in the TA with that in the remote area (RA). We used Tomo-seq, genome-wide transcriptional profiling with spatial resolution, to obtain gene expression signatures spanning from the TA to the RA. Samples from multiple sporadic TAD patients and animal models were used to validate our findings.

Results

Pathological examination revealed that the TA of TAD exhibited more pronounced intimal hyperplasia, media degeneration, and inflammatory infiltration compared to the RA. The TA also had more apoptotic cells and CD31+α-SMA+ cells. Tomo-seq revealed four distinct gene expression patterns from the TA to the RA, which were inflammation, collagen catabolism, extracellular matrix remodeling, and cell stress, respectively. The spatial distribution of genes allowed us to identify genes that were potentially relevant with TAD. NINJ1 encoded the protein-mediated cytoplasmic membrane rupture, regulated tissue remodeling, showed high expression levels in the tear area, and co-expressed within the inflammatory pattern. The use of short hairpin RNA to reduce NINJ1 expression in the beta-aminopropionitrile-induced TAD model led to a significant decrease in TAD formation. Additionally, it resulted in reduced infiltration of inflammatory cells and a decrease in the number of CD31+α-SMA+ cells. The NINJ1-neutralizing antibody also demonstrated comparable therapeutic effects and can effectively impede the formation of TAD.

Conclusions

Our study showed that Tomo-seq had the advantage of obtaining spatial expression information of TAD across the TA and the RA. We pointed out that NINJ1 may be involved in inflammation and tissue remodeling, which played an important role in the formation of TAD. NINJ1 may serve as a potential therapeutic target for TAD.