bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune disturbances in female genital tuberculosis and latent genital tuberculosis
Authors: Sharma Jai Bhagwan , Sharma Sangeeta , Sharma Eshani , Dharmendra Sona , Singh Sheena 
Published: December 2022

AbstractBackgroundFemale genital tuberculosis (FGTB), an important clinical sub‐type of extra‐pulmonary tuberculosis (EPTB) is responsible for about 10% cases of infertility in India. Both FGTB and latent genital tuberculosis (LGTB) can cause infertility through blockage of fallopian tubes and through altered uterine endometrial receptivity.AimsThis review tries to elucidates the role of various immune factors in FGTB and LGTB.ContentVarious immune disturbances are observed in FGTB and LGTB like growth factors and cytokines which inhibit implantation and several inflammatory signaling pathways like mitogen activated protein kinase (MAPK), natural killer (NK) cells, nuclear factor kappa‐B (NF‐KB), tumor necrosis factor (TNF), and toll like receptors (TLR) signaling are dysregulated. These altered immune factors and pathways may be detected in the endometrial biopsies at the early stages of disease before permanent damage. Prompt and adequate treatment with the four anti‐tubercular drugs (rifampicin [R], isoniazid [H], pyrazinamide [Z], and ethambutol [E]) can increase pregnancy rates in some of these women. Assisted reproduction especially in‐vitro fertilization and embryo transfer may be required for some women.ImplicationsInflammatory pathways identified from the gene profiling have enabled development of potential biomarkers for early diagnosis of FGTB. Immunomodulation and novel biotechniques like stem cell transplantation, nanoparticles and host directed therapies are being tried in selected patients of FGTB and LGTB with promising results.
Chlamydia trachomatis antigen induces TLR4‐TAB1‐mediated inflammation, but not cell death, in maternal decidua cells
Authors: Ortiz Briana , Driscoll Ashley , Menon Ramkumar , Taylor Brandie D. , Richardson Lauren S. 
Published: December 2022

AbstractBackgroundDuring gestation, the decidua is an essential layer of the maternal‐fetal interface, providing immune support and maintaining inflammatory homeostasis. Although Chlamydia (C.) trachomatis is associated with adverse pregnancy outcomes the pathogenic effects on maternal decidua contributing to adverse events are not understood. This study examined how C. trachomatis antigen affects cell signaling, cell death, and inflammation in the decidua.MethodsPrimary decidua cells (pDECs) from term, not‐in‐labor, fetal membrane‐decidua were cultured using the following conditions: (1) control – standard cell culture conditions, (2) 100 ng/ml or (3) 200 ng/ml of C. trachomatis antigen to model decidual cell infection in vitro. Differential expression of Toll‐like receptor (TLR) 4 (receptor for C. trachomatis antigen), signaling pathway markers phosphorylated TGF‐Beta Activated Kinase 1 (PTAB1), TAB1, phosphorylated p38 mitogen‐activated protein kinases (Pp38 MAPK), and p38 MAPK (western blot), decidual cell apoptosis and necrosis (flow cytometry), and inflammation (ELISA for cytokines) were determined in cells exposed to C. trachomatis antigen. T‐test was used to assess statistical significance (p < 0.05).ResultsC. trachomatis antigen significantly induced expression of TLR4 (p = 0.03) and activation of TAB1 (p = 0.02) compared to controls. However, it did not induce p38 MAPK activation. In addition, pDECs maintained their stromal cell morphology when exposed to C. trachomatis antigen showing no signs of apoptosis and/or necrosis but did induce pro‐inflammatory cytokine interleukin (IL)‐6 (100 ng/ml: p = 0.02 and 200 ng/ml: p = 0.03), in pDECs compared to controls.ConclusionPrenatal C. trachomatis infection can produce antigens that induce TLR4‐TAB1 signaling and IL‐6 inflammation independent of Pp38 MAPK and apoptosis and necrosis. This suggests that C. trachomatis can imbalance decidual inflammatory homeostasis, potentially contributing to adverse events during pregnancy.
Does milk of magnesia impact length of hospital stay after major colorectal resection
Authors: Tatar Cihad , Hinckley Sam , Holubar Stefan D. , Liska David , Delaney Conor P. , Steele Scott R. , Gorgun Emre 
Published: December 2022

AbstractBackgroundsMilk of magnesia (MoM) has been reported to accelerate return of bowel function following surgery. However, there is insufficient evidence regarding the impact of MoM on postoperative recovery after colorectal surgery. We aimed to determine the impact of MoM on postoperative length of stay in patients undergoing colorectal surgery.MethodsAll patients who underwent colorectal resection without an ileostomy between 2015 and 2018 were included. Patients were divided into two groups based on whether postoperative MoM (MoM) was administered or not, according to surgeons' prescribing preferences. Consecutive patients of surgeons who prescribe MoM were included in the MoM group, while consecutive patients of surgeons who prefer not to prescribe MoM served as the control group. Age, gender, preoperative comorbidities, surgical approach, length of stay, readmission, postoperative complications and mortality were evaluated and compared between the groups.ResultsA total of 3292 patients were included; 523 (15.9%) patients were prescribed MoM. Patients in the MoM group were found to be significantly older, with higher BMI and ASA class, and more often undergoing operations for cancer resection or colostomy creations, than the control group. Postoperative complications were comparable between the groups. On multivariable linear regression, MoM use was associated with a 14.1% reduction in length of stay (MoM group 4 (2; 8), control group 5 (3; 8 P = 0.006)).ConclusionMoM as adjunct medication in the postoperative period following colorectal surgery is associated with reduced length of stay, without an increase in postoperative complications.
Detection of physiological control inputs preload and afterload from intrinsic pump parameters in total artificial heart
Authors: Kirn Borut , Diedrich Mario , Schmitz‐Rode Thomas , Steinseifer Ulrich , Jansen Sebastian V. 
Published: December 2022

AbstractBackgroundIn the total artificial heart (TAH), the inputs to the physiological control unit, preload, and afterload, are detected from intrinsic pump parameters (e.g., motor current). Within this study, their detection techniques are developed, and their reliability in pre‐ and afterload prediction is mapped for a broad range of cardiovascular system states.MethodsWe used ReinHeart TAH which is a fully implantable TAH with a plunger coil drive that is alternately emptying the left and right chambers. From the coil currents we first derived a force generated by the piston with respect to its position and then analyzed its pattern to detect (1) preload—chamber filling, found as piston position at begin ejection and (2) afterload—mean outflow pressures, determined as linearly calibrated average piston force during ejection. TAH is then integrated into a mock loop circulation (MLC) which is set to 135 different steady operating points varying in chamber filling (0%–100%, five steps), mean outflow pressures (system circulation: 60–90–120 mm Hg, pulmonary circulation: 15–30‐45 mm Hg), and heart cycle duration (171–600 ms in seven non‐equidistant steps). The detected preload and afterload are compared to MLC set values, and the errors are mapped.ResultsRespectively for the left and right chambers, the preload was detectable in 134 and 118 operating points and the mean error was ±3% and ±2%. The afterload was detectable in 135 and 87 operating points and the mean error was 37% and 30% respectively for left and right circulation. The operational points that are further away from homeostatic equilibrium values generally yielded larger errors. The largest errors were observed for right circulation at long cycle duration, low afterload, and low filling.ConclusionsThe study yields reliable preload estimation in a broad range of physiological states, particularly for left circulation. Detection of afterload needs further improvements. The study revealed a need for piston movement optimization within the ReinHeart TAH during the early phase of systole.
Faecal microbiota transplantation for recurrent C. difficile infections: challenges and improvement opportunities for clinical practice and healthcare systems
Authors: Hocking Lucy , Ianiro Gianluca , Leong Rupert W. , Iqbal Tariq , Kao Dina , Cabling Mark , Stockwell Stephanie , Romanelli Robert J. , Marjanovic Sonja 
Published: December 2022

SummaryBackgroundThere is growing interest in faecal microbiota transplantation (FMT) as a treatment for recurrent Clostridioides difficile infection (CDI), but evidence on the diverse requirements for safe, effective and accessible services is fragmented and limited.AimsTo identify key components of FMT provision relating to the patient care pathway, stool donor pathway and wider healthcare system, and to explore variation in practiceMethodsWe conducted a narrative review of the literature and consultations with key clinical experts in the field. Evidence is drawn from high‐income country contexts, with an emphasis on Australia, Canada, Italy and the United Kingdom as case example countries.ResultsWe identify and discuss key challenges to do with healthcare capacity (workforce, FMT and stool banking facilities), donors and donations, patient access and choice of FMT delivery routes, regulation, costs and reimbursement. We also identify improvement opportunities to increase awareness of FMT and referral processes, physician training, maintaining patient registries and outcome monitoring metrics, in‐country regulatory harmonisation and tackling reimbursement challenges and discuss future research needs.ConclusionEffectively bringing FMT to patients in a healthcare system requires much more than just the existence of a clinically effective procedure. With FMT being a potentially effective treatment option for recurrent CDI for many patients, a well‐rounded understanding of how appropriate FMT capacity can be built and nurtured is important for both healthcare providers and policymakers seeking to improve patient care.
A proof‐of‐concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease
Authors: Gamez Josep , Calopa Matilde , Muñoz Esteban , Ferré Aileen , Huertas Oscar , McAllister Kevin , Reig Núria , Scart‐Grès Catherine , Insa Raúl , Kulisevsky Jaime 
Published: December 2022

AimsThe study's aim is to investigate the efficacy and safety of SOM3355 (bevantolol hydrochloride), a β1‐adrenoreceptor antagonist with recently identified vesicular monoamine transporter type 2 inhibitory properties, as a repositioned treatment to reduce chorea in Huntington's disease (HD).MethodsA randomized, placebo‐controlled proof‐of‐concept study was performed in 32 HD patients allocated to 2 arms of 4 sequential 6‐week periods each. Patients received placebo and SOM3355 at 100 and 200 mg twice daily in a crossover design. The primary endpoint was improvement by at least 2 points in the total maximal chorea score in any active drug period compared with the placebo period.ResultsThe primary endpoint was met in 57.1% of the patients. Improvements ≥3, ≥4, ≥5 and ≥6 points vs. placebo treatment were observed in 28.6, 25.0, 17.9 and 10.7% of the patients, respectively. A mixed‐model analysis found a significant improvement in the total maximal chorea score of −1.14 (95% confidence interval, −2.11 to −0.16; P = .0224) with 200 mg twice daily SOM3355 treatment compared with placebo treatment. These results were paralleled by Clinical and Patient Global Impression of Change ratings (secondary endpoints). An elevation in plasma prolactin levels by 1.7–1.9‐fold was recorded (P < .005), probably reflecting the effect on the dopamine pathway, consistent with vesicular monoamine transporter type 2 inhibition. The most frequent adverse events during SOM3355 administration were mild to moderate.ConclusionWithin the limits of this study, the results suggest that SOM3355 reduces chorea in patients with HD and is well‐tolerated. Larger studies are necessary to confirm its therapeutic utility as an antichoreic drug.EudraCT number: 2018–000203‐16 and ClinicalTrials.gov Identifier: NCT03575676.
Time‐to‐event surrogate end‐points in multiple myeloma randomised trials from 2005 to 2019: A surrogacy analysis
Authors: Etekal Tommy , Koehn Kelly , Sborov Douglas W. , McClune Brian , Prasad Vinay , Haslam Alyson , Berger Katherine , Booth Christopher , Al Hadidi Samer , Abdallah Al‐Ola , Goodman Aaron , Mohyuddin Ghulam Rehman 
Published: December 2022

SummaryUse of surrogate end‐points such as progression‐free survival (PFS) and other time‐to‐event (TTE) end‐points is common in multiple myeloma (MM) clinical trials. This systematic review characterises all published randomised controlled trials (RCTs) in MM using PFS or other TTE end‐points between 2005 and 2019 and assesses strength of surrogacy of PFS for overall survival (OS). The association between OS hazard ratios (HRs) and PFS HRs was evaluated with linear regression, and the coefficient of determination with Pearson's correlation. We identified 88 RCTs of which 67 (76%) used PFS as the primary/co‐primary end‐point. One trial indicated whether progression was biochemical or clinical. Of the variance in OS, 39% was due to variance in PFS. Correlation between PFS and OS was weak (0.62, 95% confidence interval [CI] 0.38–0.78). In newly diagnosed MM, 43% of the variance in OS was due to changes in PFS. The correlation between PFS and OS was weak (0.65, 95% CI 0.30–0.84). In relapsed/refractory MM, 58% of the variance in OS was due to changes in PFS. Correlation between PFS and OS was medium (0.76, 95% CI 0.42–0.91). We demonstrate that PFS and progression characteristics are characterised poorly in MM trials and that PFS is a poor surrogate for OS in MM.
Median 5‐year outcomes of primary focal irreversible electroporation for localised prostate cancer
Authors: Scheltema Matthijs J. , Geboers Bart , Blazevski Alexandar , Doan Paul , Katelaris Athos , Agrawal Shikha , Barreto Daniela , Shnier Ron , Delprado Warick , Thompson James E. , Stricker Phillip D. 
Published: December 2022

AbstractObjectivesTo evaluate longer‐term oncological and functional outcomes of focal irreversible electroporation (IRE) as primary treatment for localised clinically significant prostate cancer (csPCa) at a median follow‐up of 5 years (up to 10 years).Patients and MethodsAll patients that underwent focal IRE as primary treatment for localised PCa between February 2013 and August 2021 with a minimum 12 months of follow‐up were analysed. Follow‐up included 6‐month magnetic resonance imaging (MRI) and standardised transperineal saturation template ± targeted biopsies at 12 months, and further biopsies in the case of clinical suspicion on serial imaging and/or prostate‐specific antigen (PSA) levels. Failure‐free survival (FFS) was defined as no progression to radical treatment or nodal/distant disease. Local recurrence was defined as any International Society of Urological Pathology Grade of ≥2 on biopsy.ResultsA total of 229 patients were analysed with a median (interquartile range [IQR]) follow‐up of 60 (40–80) months. The median (IQR) age was 68 (64–74) years, the median (IQR) PSA level was 5.9 (4.1–8.2) ng/mL, and 86% harboured intermediate‐risk disease and 7% high‐risk disease. In all, 38 patients progressed to radical treatment (17%), at a median (IQR) of 35 (17–53) months after IRE. Kaplan–Meier FFS rates were 91% at 3 years, 84% at 5 years and 69% at 8 years. Metastasis‐free survival was 99.6% (228/229), PCa‐specific and overall survival were 100% (229/229). Residual csPCa was found in 24% (45/190) during follow‐up biopsy and MRI showed a complete ablation in 82% (186/226). Short‐term urinary continence was preserved (98%, three of 144 at baseline, 99%, one of 131 at 12 months) and erections sufficient for intercourse decreased by 13% compared to baseline (71% to 58%).ConclusionLonger‐term follow‐up confirms our earlier findings that focal IRE provides acceptable local and distant oncological control in selected men with less urinary and sexual toxicity than radical treatment. Long‐term follow‐up and external validation of these findings, is required to establish this new treatment paradigm as a valid treatment option.
Kinetic analysis of endogenous β2‐adrenoceptor‐mediated cAMP GloSensor™ responses in HEK293 cells
Authors: Cullum Sean A. , Veprintsev Dmitry B. , Hill Stephen J. 
Published: December 2022

AbstractBackground and AimStandard pharmacological analysis of agonist activity utilises measurements of receptor‐mediated responses at a set time‐point, or at the peak response level, to characterise ligands. However, the occurrence of non‐equilibrium conditions may dramatically impact the properties of the response being measured. Here we have analysed the initial kinetic phases of cAMP responses to β2‐adrenoceptor agonists in HEK293 cells expressing the endogenous β2‐adrenoceptor at extremely low levels.Experimental ApproachThe kinetics of β2‐adrenoceptor agonist‐stimulated cAMP responses were monitored in real‐time, in the presence and absence of antagonists, in HEK293 cells expressing the cAMP GloSensor™ biosensor. Potency (EC50) and efficacy (Emax) values were determined at the peak of the agonist GloSensor™ response and compared to kinetic parameters L50 and IRmax values derived from initial response rates.Key ResultsThe partial agonists salbutamol and salmeterol displayed reduced relative IRmax values (with respect to isoprenaline) when compared with their Emax values. Except for the fast dissociating bisoprolol, preincubation with β2‐adrenoceptor antagonists produced a large reduction in the isoprenaline peak response due to a state of hemi‐equilibrium in this low receptor reserve system. This effect was exacerbated when IRmax parameters were measured. Furthermore, bisoprolol produced a large reduction in isoprenaline IRmax consistent with its short residence time.Conclusions and ImplicationsKinetic analysis of real‐time signalling data can provide valuable insights into the hemi‐equilibria that can occur in low receptor reserve systems with agonist–antagonist interactions, due to incomplete dissociation of antagonist whilst the peak agonist response is developing.
Schools engaged in doom‐monitoring students' online interactions and content creation: an analysis of dominant media discourses
Authors: Kikerpill Kristjan , Siibak Andra 
Published: December 2022

BackgroundGrowing public concern about the safety and security of schools has led many schools and school districts within the United States to hire private companies to monitor students' online interactions and the content they create, including on social media. The use of such technologies supposedly increases schools' awareness of what students are doing online and, thus, helps to identify and prevent potential issues such as mental health problems, cyberbullying, or self‐harm that might otherwise go unnoticed. However, there is currently no evidence to support that social media surveillance or content monitoring is able to effectively address these public health and safety issues.MethodsThus, our study explores how the different voices present in the discourse – students, school officials, privacy advocates, and service providers' representatives – justify or condemn the surveillance of student‐produced online content in publicly available news media articles. We adopt a critical discursive psychology approach to study news articles, which were published in international media in the last 3 years (2019 N = 53; 2020 N = 56; 2021 N = 77), reporting on the use of digital surveillance technologies targeting student‐produced content.Results and conclusionsThree dominant interpretive repertoires emerged from the analyzed news media articles: ‘silenced students, expert adults’, ‘a solution in search of a problem’, and ‘the normalization of surveillance for a good cause’. Our findings show that, under the auspices of protecting children, schools are actively engaged in ‘doom‐monitoring’, which is the indiscriminate and inaccurate surveillance of people in anticipation of the next bad thing. The opinions and views of adults, including school officials, vendors, and civil liberties advocates, dominate over the voices of students.
Aetiology of occupational hand eczema in hairdressers: Tackling the complexity of exposure combinations to identify patterns associated with increased risk of hand eczema
Authors: Havmose Martin S. , Uter Wolfgang , Gefeller Olaf , Johansen Jeanne D. 
Published: December 2022

AbstractIntroductionHairdressers are exposed to wet work and manifold allergens at work, rendering exposure complex and the aetiology of occupational hand eczema (OHE) often multifactorial in this occupational group.ObjectivesTo identify exposure patterns associated with increased risk of hand eczema in hairdressers.MethodsAll hairdressers graduating from 2004 to 2007 and 2015 to 2018 received a questionnaire in 2009 and 2020, respectively. Current exposures (with or without regular glove use) and OHE were self‐reported, and their association examined. Patterns of exposure were identified by latent class analysis (LCA).ResultsA total response of 39.9% (668/1675) was obtained. Six exposure profiles (#1–6) were identified by LCA across 11 tasks performed with or without gloves as well as deep conditioning, that is, 23 task items. Compared to profile #1 with the lowest OHE risk (reference) an increased risk of current OHE were seen in profile #4 [adjusted odds ratio [aOR] 6.5, 95% confidence interval [CI] 1.5–44.8 and #6 (aOR 39.4, 95%CI 6.1–362.8)] in logistic regression analysis. Profile #1 and #6 had performed the same tasks, but in profile #6 regular glove use was performed in 9.1% (1/ 11) of tasks compared to 72.7% (8/11) of tasks in profile #1 (p = 0.002).ConclusionAlthough occupational exposures in hairdressing are complex, meaningful patterns associated with a wide range of OHE risk can be identified by LCA. The increase of OHE risk seems predominantly to be due to poor compliance with protective gloves. LCA could be applied to further fields of complex (skin) exposures.
Impact of faecal haemoglobin based triage of bowel symptoms presenting to primary care on colorectal cancer diagnosis
Authors: Delson Dwi , Ward Mark , Haddock Rosemary , Nobes Jennifer , Digby Jayne , Strachan Judith A. , Mowat Craig 
Published: December 2022

AbstractAimFaecal immunochemical testing (FIT) for faecal haemoglobin was introduced into primary care in National Health Service Tayside in 2015 as an adjunct to clinical assessment of new bowel symptoms. We aimed to assess the impact of FIT‐based triage in primary care on colorectal cancer (CRC) diagnosis.MethodCancer audit data between January 2016 and December 2019 were reviewed to identify all patients diagnosed locally with CRC. The mode of presentation and stage at diagnosis were noted and patient records were interrogated to identify whether FIT and full blood count (FBC) had been performed prior to referral. Results were compared between the FIT and non‐FIT groups.ResultsIn all, 1245 patients were diagnosed with CRC of whom 581 (46.7%) presented through primary care. FIT was performed prior to referral in 440/581 (75.7%), with the proportion increasing from 62.3% in 2016 to 85.8% in 2019. At faecal haemoglobin ≥10 μg Hb/g faeces, sensitivity for CRC was 94.1%. Over the study period the annual proportion of non‐emergency presentations increased significantly; presentations from primary care increased from 43.1% to 53.5% (P = 0.0096). After excluding non‐FIT patients who had an overt CRC at referral, there was no difference in stage at diagnosis between FIT and non‐FIT cancers. Safety‐netting with FBC was widely used in our cohort with 97.3% of FIT patients having also had FBC.ConclusionFIT‐based triage of new bowel symptoms in primary care is associated with increased non‐emergency presentation of CRC but this did not influence stage at diagnosis.