bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shengjiang San alleviated sepsis-induced lung injury through its bidirectional regulatory effect
Authors: Yan Shifan , Jiang Yu , Yu Ting , Hou Changmiao , Xiao Wen , Xu Jing , Wen Huili , Wang Jingjing , Li Shutong , Chen Fang , Li Shentang , Liu Xiehong , Tan Hao , Zou Lianhong , Liu Yanjuan , Zhu Yimin 
Published: April 2023

Abstract
Background
Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection, for which effective therapeutic strategies are still absent. Shengjiang San (SJS), a well-known Traditional Chinese Medicine formula, has been widely used clinically. However, its role in sepsis-induced lung injury remains unclear.

Methods
To explore its specific mechanism, we firstly established a sepsis animal model using cecal ligation and puncture (CLP) and treated MH-S cells with LPS plus ATP. Then, UPLC/Q-TOF–MS/MS was utilized to identify its active ingredients. Network pharmacology analysis was performed to uncover the potential mechanism. HE staining and biochemical analysis were conducted to validate its therapeutic effect. ELISA was applied to detect the release of pro-inflammatory and anti-inflammatory cytokines. Western blot was utilized to detect the protein levels of GSDMD, NLRP3, P65, ASC and caspase-1.

Results
SJS could dramatically increase the survival rate of sepsis. In addition, it is able to inhibit the pro-inflammatory cytokines release at day 1 post CLP while promote their production at day 7, indicating SJS could attenuate uncontrolled inflammatory response in the early stage and improve immunosuppression in the late phase. Network pharmacology analysis showed that pyroptosis is the crucial action SJS exerted in the protection of sepsis-induced lung injury. Western blot data implicated SJS could attenuate pyroptosis in early sepsis while enhance in the late phase.

Conclusions
SJS acted to alleviate sepsis-induced lung injury through its bidirectional regulatory effect.
How do patients and other members of the public engage with the orphan drug development? A narrative qualitative synthesis
Authors: Frost Julia , Hall Abi , Taylor Emily , Lines Sarah , Mandizha Jessica , Pope Catherine 
Published: April 2023

Abstract
Background
The diversity of patient experiences of orphan drug development has until recently been overlooked, with the existing literature reporting the experience of some patients and not others. The current evidence base (the best available current research) is dominated by quantitative surveys and patient reported outcome measures defined by researchers. Where research that uses qualitative methods of data collection and analysis has been conducted, patient experiences have been studied using content analysis and automatic textual analysis, rather than in-depth qualitative analytical methods. Systematic reviews of patient engagement in orphan drug development have also excluded qualitative studies. The aim of this paper is to review qualitative literature about how patients and other members of the public engage with orphan drug development.

Methods
We conducted a systematic search of qualitative papers describing a range of patient engagement practices and experiences were identified and screened. Included papers were appraised using a validated tool (CASP), supplemented by reporting guidance (COREQ), by two independent researchers.

Results
262 papers were identified. Thirteen papers reported a range of methods of qualitative data collection. Many conflated patient and public involvement and engagement (PPIE) with qualitative research. Patients were typically recruited via their physician or patient organisations. We identified an absence of overarching philosophical or methodological frameworks, limited details of informed consent processes, and an absence of recognisable methods of data analysis. Our narrative synthesis suggests that patients and caregivers need to be involved in all aspects of trial design, including the selection of clinical endpoints that capture a wider range of outcomes, the identification of means to widen access to trial participation, the development of patient facing materials to optimise their decision making, and patients included in the dissemination of trial results.

Conclusions
This narrative qualitative synthesis identified the explicit need for methodological rigour in research with patients with rare diseases (e.g. appropriate and innovative use of qualitative methods or PPIE, rather than their conflation); strenuous efforts to capture the perspectives of under-served, under-researched or seldom listened to communities with experience of rare diseases (e.g. creative recruitment and wider adoption of post-colonial practices); and a re-alignment of the research agenda (e.g. the use of co-design to enable patients to set the agenda, rather than respond to what they are being offered).
Imaging ovarian cancer – from baseline characteristics to high-risk image factors
Authors: Sartor Hanna , Bjurberg Maria , Asp Mihaela , Kahn Anna , Brändstedt Jenny , Kannisto Päivi , Jirström Karin 
Published: April 2023

Abstract
Background
Imaging ovarian cancer (OC) includes evaluating peritoneal carcinomatosis (PC) and enlarged cardio phrenic lymph nodes (CPLN) by computed tomography (CT), and thorough evaluation is tedious work. A “CT short score” with high-risk CT parameters might be a more pragmatic approach, but it is not known if such a short score associates with aggressive OC subtypes and impaired OC survival. Further, it is not known if certain established OC risk factors are linked to high-risk CT-findings which would be important in image evaluation. Herein, we investigate a CT short score and its relation to baseline characteristics, OC subtypes, and survival.

Methods
The Malmö Diet and Cancer Study is a prospective cohort that included 17,035 women (1991–1996). Baseline characteristics and tumor information on 159 OC and information on OC specific survival (last follow-up, 2017-12-31) was registered. A CT short score (CPLN and PC-index (PCI) in seven regions) was registered and associations with clinical stage [stage I vs. advanced stage (II-IV), histological type/grade (high grade serous and endometrioid vs. other subtypes], and OC-specific survival were analyzed with logistic and Cox regression, respectively. Parity and menopausal status were analyzed in relation to short score and PCI.

Results
There was an association between higher short score and advanced clinical stage (adjusted OR 2.76 (1.42—5.38)), adjusted for age at diagnosis and histological type/grade. Higher short score was associated with impaired OC specific survival (adjusted HR 1.17 (1.01—1.35)), adjusted for age at diagnosis, histological type/grade, and clinical stage. There were no significant associations between parity, menopausal status, and short score/PCI.

Conclusions
CT short score was significantly associated with advanced clinical stages and impaired OC survival. A pragmatic approach (based on CT) to evaluate high risk image findings in OC could help reduce radiologists’ workload and at the same time provide structured reports to surgeons and oncologists involved in OC care.
Targeting DCLK1 attenuates tumor stemness and evokes antitumor immunity in triple-negative breast cancer by inhibiting IL-6/STAT3 signaling
Authors: Liu Heshu , Yan Rui , Xiao Zeru , Huang Xuying , Yao Jiannan , Liu Jian , An Guangyu , Ge Yang 
Published: April 2023

AbstractTriple-negative breast cancer (TNBC) exhibits the poorest outcomes among breast cancer subtypes due to the high heterogeneity and a lasting scarcity of effectual treatments. Targeted therapies based on molecular subtypes of TNBC are critical step toward tailoring treatments to improve clinical outcomes. Gastrointestinal cancer stem cell (CSC) marker DCLK1 was reported to be highly expressed in stem cell-rich subtype of TNBC. Here, we firstly explored the impacts of DCLK1 on tumor cells as well as their immune microenvironment in TNBC and potential therapeutic strategies for TNBC patients with high DCLK1 expression. Our results disclosed that DCLK1 overexpression promoted, while knockout of DCLK1 suppressed the CSC-like traits of TNBC cells and resistance to chemotherapeutics. Besides, DCLK1 supported immune escape by inhibiting intratumoral cytotoxic T cell infiltration in TNBC and hence limited immune checkpoint inhibitors efficacy. Mechanistically, bioinformatics analysis revealed that IL-6/STAT3 signaling was significantly enriched in high DCLK1-expressing patients, and our results further revealed that DCLK1 enhanced IL-6 expression and STAT3 activation in TNBC cells, which finally gave rise to upregulated CSC traits and suppressed CD8+ T-cell activity. Inhibiting IL-6/STAT3 pathway by IL-6R antagonist, Tocilizumab or STAT3 inhibitor, S31-201 could abolish DCLK1-promoted malignant phenotypes of TNBC cells. Finally, DCLK1 was identified to be specifically and highly expressed in the mesenchymal-like subtype of TNBC and targeting DCLK1 could improve chemotherapy efficacy and activate antitumor immunity. Overall, our study revealed the potential clinical benefits of targeting DCLK1 in TNBC treatment.
A cluster randomised trial to evaluate the effectiveness of household alcohol-based hand rub for the prevention of sepsis, diarrhoea, and pneumonia in Ugandan infants (the BabyGel trial): a study protocol
Authors: Chebet Martin , Mukunya David , Burgoine Kathy , Kühl Melf-Jakob , Wang Duolao , Medina-Lara Antonieta , Faragher Eric Brian , Odiit Amos , Olupot-Olupot Peter , Stadskleiv Engebretsen Ingunn Marie , Waniaye John Baptist , Wandabwa Julius , Tylleskär Thorkild , Weeks Andrew 
Published: April 2023

Abstract
Background
Infections are one of the leading causes of death in the neonatal period. This trial aims to evaluate if the provision of alcohol-based hand rub (ABHR) to pregnant women for postnatal household use prevents severe infections (including sepsis, diarrhoea, pneumonia, or death) among infants during the first three postnatal months.

Methods
Through a cluster-randomised trial in eastern Uganda, 72 clusters are randomised in a 2-arm design with rural villages as units of randomisation. We estimate to include a total of 5932 pregnant women at 34 weeks of gestation. All women and infants in the study are receiving standard antenatal and postnatal care. Women in the intervention group additionally receive six litres of ABHR and training on its use. Research midwives conduct follow-up visits at participants’ homes on days 1, 7, 28, 42, and 90 after birth and telephone calls on days 14, 48, and 60 to assess the mother and infant for study outcomes. Primary analyses will be by intention to treat.

Discussion
This study will provide evidence on the effectiveness of a locally available and low-cost intervention in preventing neonatal sepsis and early infant infections. If ABHR is found effective, it could be implemented by adding it to birthing kits.

Trial registration
Pan African Clinical Trial Registry, PACTR202004705649428. Registered 1 April 2020, https://pactr.samrc.ac.za/.
No evidence for schistosome parasite fitness trade-offs in the intermediate and definitive host
Authors: Le Clec’h Winka , Chevalier Frédéric D. , Jutzeler Kathrin , Anderson Timothy J. C. 
Published: April 2023

Abstract
Background
The trematode parasite Schistosoma mansoni uses an aquatic snail intermediate and a vertebrate definitive host to complete its life cycle. We previously showed that a key transmission trait—the number of cercariae larvae shed from infected Biomphalaria spp. snails—varies significantly within and between different parasite populations and is genetically controlled by five loci. We investigated the hypothesis that the success of parasite genotypes showing high propagative fitness in the intermediate snail host may be offset by lower reproductive fitness in the definitive vertebrate host.

Methods
We investigated this trade-off hypothesis by selecting parasite progeny producing high or low number of larvae in the snail and then comparing fitness parameters and virulence in the rodent host. We infected inbred BALB/c mice using two Schistosoma mansoni parasite lines [high shedder (HS) and low shedder (LS) lines] isolated from F2 progeny generated by genetic crosses between SmLE (HS parent) and SmBRE (LS parent) parasites. We used the F3 progeny to infect two populations of inbred Biomphalaria glabrata snails. We then compared life history traits and virulence of these two selected parasite lines in the rodent host to understand pleiotropic effects of genes determining cercarial shedding in parasites infecting the definitive host.

Results
HS parasites shed high numbers of cercariae, which had a detrimental impact on snail physiology (measured by laccase-like activity and hemoglobin rate), regardless of the snail genetic background. In contrast, selected LS parasites shed fewer cercariae and had a lower impact on snail physiology. Similarly, HS worms have a higher reproductive fitness and produced more viable F3 miracidia larvae than LS parasites. This increase in transmission is correlated with an increase in virulence toward the rodent host, characterized by stronger hepato-splenomegaly and hepatic fibrosis.

Conclusions
These experiments revealed that schistosome parasite propagative and reproductive fitness was positively correlated in intermediate and definitive host (positive pleiotropy). Therefore, we rejected our trade-off hypothesis. We also showed that our selected schistosome lines exhibited low and high shedding phenotype regardless of the intermediate snail host genetic background. ​

Graphical Abstract
Diagnostic yield of genetic screening in a diverse, community-ascertained cohort
Authors: Rao Nandana D. , Kaganovsky Jailanie , Malouf Emily A. , Coe Sandy , Huey Jennifer , Tsinajinne Darwin , Hassan Sajida , King Kristine M. , Fullerton Stephanie M. , Chen Annie T. , Shirts Brian H. 
Published: April 2023

Abstract
Background
Population screening for genetic risk of adult-onset preventable conditions has been proposed as an attractive public health intervention. Screening unselected individuals can identify many individuals who will not be identified through current genetic testing guidelines.

Methods
We sought to evaluate enrollment in and diagnostic yield of population genetic screening in a resource-limited setting among a diverse population. We developed a low-cost, short-read next-generation sequencing panel of 25 genes that had 98.4% sensitivity and 99.98% specificity compared to diagnostic panels. We used email invitations to recruit a diverse cohort of patients in the University of Washington Medical Center system unselected for personal or family history of hereditary disease. Participants were sent a saliva collection kit in the mail with instructions on kit use and return. Results were returned using a secure online portal. Enrollment and diagnostic yield were assessed overall and across race and ethnicity groups.

Results
Overall, 40,857 people were invited and 2889 (7.1%) enrolled. Enrollment varied across race and ethnicity groups, with the lowest enrollment among African American individuals (3.3%) and the highest among Multiracial or Other Race individuals (13.0%). Of 2864 enrollees who received screening results, 106 actionable variants were identified in 103 individuals (3.6%). Of those who screened positive, 30.1% already knew about their results from prior genetic testing. The diagnostic yield was 74 new, actionable genetic findings (2.6%). The addition of more recently identified cancer risk genes increased the diagnostic yield of screening.

Conclusions
Population screening can identify additional individuals that could benefit from prevention, but challenges in recruitment and sample collection will reduce actual enrollment and yield. These challenges should not be overlooked in intervention planning or in cost and benefit analysis.
Successful management of poisoning with ivermectin (Mectizan) in the Obala health district (Centre Region, Cameroon): a case report
Authors: Donfo-Azafack Cyrille , Nana-Djeunga Hugues C. , Wafeu-Sadeu Guy , Dongmo-Yemele Raïssa , Kamgno Joseph 
Published: April 2023

Abstract
Background
Ivermectin (Mectizan) is an anthelmintic drug that plays a major role in the fight against two major filarial diseases, onchocerciasis and lymphatic filariasis. Unlike previous drugs that had serious and sometimes fatal side effects, ivermectin has been considered to be safe and, therefore, is widely used. Data reporting the clinical presentation of poisoning with ivermectin are very scanty, even in experimental studies.

Case presentation
In this paper, we report the case of a 19-year-old Black African female student residing in Obala (Centre Region, Cameroon) who was admitted to a health facility in Central Cameroon for a neurological disorder after intoxication with about 400 tablets of ivermectin 3 mg (~100 times the standard doses). This neurological disorder was characterized by somnolence, kinetic ataxia, increase of tendon reflex, and central visual disturbance. Management of this intoxication consisted of symptomatic treatment and monitoring of hemodynamic parameters for 5 days, with a favorable course.

Conclusions
This is the first report of a poisoning with ivermectin at ~100 times the recommended dose. This case report confirms the safety and tolerability of ivermectin, even at exceptionally high dose.
“I’m 'just' a community pediatrician” views and challenges of pediatricians working in the community in Israel
Authors: Pinchover Shulamit , Berger-Raanan Rony , Yaari Maya , Rudolf Mary , Rubin Lisa , Idan-Prusak Dafna , Skvirsky Vera , Margolin Tirzah , Gadassi Hava 
Published: April 2023

Abstract
Background
There are ongoing changes around the world in the training and practice of pediatricians who work in the community. These changes are driven by the understanding that pediatricians are required to provide not only acute primary care but also to address more comprehensive concerns, particularly the ‘new morbidities’. The present study examines the professional identity of Israeli pediatricians in the community in light of these changes, the barriers and challenges to their work and professional adaptations in the field.

Methods
We used a mixed-methods approach, collecting the perspectives of 137 pediatricians who work in the community through an anonymous online survey, followed by in-depth semi-structured interviews with 11 community pediatricians.

Results
The survey results show that community pediatricians in Israel have limited knowledge on a variety of developmental, behavioral and emotional issues; that they lack working relationships with medical or other professionals; and are rarely engaged with other community services. Three main themes arose from the interviews that support and deepen the survey results: perceptions of the profession (pediatrics in the community vs. community pediatrics), the stature of pediatricians in the community (during residency, the choice to work in the community, their daily work) and barriers and change in community pediatrics (isolation, limited resources and challenges arising from the nature of community work).

Conclusions
The present study sheds light on the professional identity and the day-to-day challenges and successes of pediatricians working in the community. Continuing medical education, providing a supportive framework and professional community, better resources, more time with patients, and tools and opportunities for professional development would help pediatricians who work in the community to overcome some of these challenges. The research findings reinforce the need for policy change in the field of community pediatrics with a specific community training curriculum, provision of more resources and ongoing support for pediatricians. This requires partnership between the HMOs, the Ministry of Health, the Scientific Council (Israel Medical Association, professional organizations) and NGOs in order to turn individual-level solutions into system-level and policy-changing solutions.
Sialic acid exacerbates gut dysbiosis-associated mastitis through the microbiota-gut-mammary axis by fueling gut microbiota disruption
Authors: Zhao Caijun , Hu Xiaoyu , Qiu Min , Bao Lijuan , Wu Keyi , Meng Xiangyue , Zhao Yihong , Feng Lianjun , Duan Shiyu , He Yuhong , Zhang Naisheng , Fu Yunhe 
Published: April 2023

AbstractBackgroundMastitis is one of the most severe diseases in humans and animals, especially on dairy farms. Mounting evidence indicates that gastrointestinal dysbiosis caused by induction of subacute ruminal acidosis (SARA) by high-grain diet consumption and low in dietary fiber is associated with mastitis initiation and development, however, the underlying mechanism remains unknown.ResultsIn the present study, we found that cows with SARA-associated mastitis have altered metabolic profiles in the rumen, with increased sialic acids level in particular. Consumption of sialic acid (SA) in antibiotic-treated mice, but not healthy mice, induced marked mastitis. SA treatment of antibiotic-treated mice also induced mucosal and systemic inflammatory responses, as evidenced by increased colon and liver injuries and several inflammatory markers. In addition, gut dysbiosis caused by antibiotic impaired gut barrier integrity, which was aggravated by SA treatment. SA potentiated serum LPS level caused by antibiotic treatment, leading to increased activation of the TLR4-NF-κB/NLRP3 pathways in the mammary gland and colon. Moreover, SA facilitated gut dysbiosis caused by antibiotic, and especially enhancedEnterobacteriaceaeandAkkermansiaceae, which correlated with mastitis parameters. Fecal microbiota transplantation from SA-antibiotic-treated mice mimicked mastitis in recipient mice. In vitro experiments showed that SA promptedEscherichia coligrowth and virulence gene expression, leading to higher proinflammatory cytokine production in macrophages. Targeting the inhibition ofEnterobacteriaceaeby sodium tungstate or treating with the commensalLactobacillus reuterialleviated SA-facilitated mastitis. In addition, SARA cows had distinct ruminal microbial structure by the enrichment of SA-utilizing opportunistic pathogenicMoraxellaceaeand the depletion of SA-utilizing commensalPrevotellaceae. Treating mice with the specific sialidase inhibitor zanamivir reduced SA production andMoraxellaceaeabundance, and improved mastitis in mice caused by ruminal microbiota transplantation from cows with SARA-associated mastitis.ConclusionsThis study, for the first time, indicates that SA aggravates gut dysbiosis-induced mastitis by promoting gut microbiota disturbance and is regulated by commensal bacteria, indicating the important role of the microbiota-gut-mammary axis in mastitis pathogenesis and suggesting a potential strategy for mastitis intervention based on gut metabolism regulation.