Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychosocial factors at work and fertility and menstrual disorders: a systematic review

Objective: This systematic review aimed to evaluate the association between psychosocial factors at work and menstrual abnormalities or fertility by collecting the literature that had utilized a longitudinal or prospective cohort design. Data sources: MEDLINE, EMBASE, PsycINFO, PsycARTICLES, and Japan Medical Abstracts Society electronic databases were searched for published studies from inception to 26th February 2020. Study eligibility criteria: The inclusion criteria for this systematic review were defined as follows: (P) Adult female workers (over 18 years old), (E) Presence of adverse psychosocial factors at work, (C) Absence of adverse psychosocial factors at work, and (O) Any menstrual cycle disorders, menstrual-related symptoms, or fertility. The study design was limited to prospective/longitudinal studies. Study appraisal and synthesis methods: The included studies were descriptively summarized in a narrative format. Results: Database searching yielded 12,868 abstracts. After the screening process, six studies were included. The outcomes were fertility (n=3), early menopause (n=1), endometriosis (n=1), and serum hormones (n=1). Three included studies presented significant findings: women with high job demands were significantly less likely to conceive; working over 40 hours per week and lifting or moving a heavy load >15 times per day significantly increased the duration of pregnancy attempts; women with rotating night shift work had increased risk of earlier menopause. All the study (n=3) that examined the association of night shift/rotating work with fertility outcomes showed no significant difference. No study investigated the association of psychosocial factors at work with menstrual abnormality. Conclusion: This review revealed insufficient high-level evidence on the association of psychosocial factors at work with fertility and menstrual disorders. Future well-designed studies are needed. Trial registration: The study protocol was registered at the UMIN registry (registration number: UMIN000039488). The registration date is 14th Feb 2020. URL: https://upload.umin. ac.jp/cgi-bin/ctr/ctr_view_reg. cgi? recptno=R000044704 Review protocol: Protocol paper is available in preprint format. URL:https://assets.researchsquare. com/files/rs-179301/v1/48845b10-5ec4-4d48-8918-3dcf0e0edded.pdf? c=1631873381
Decision Delay Is a Significant Contributor to Prehospital Delay for Stroke Symptoms

Prehospital delay after stroke symptom onset is a primary barrier to eligibility for reperfusion therapies. Decision delay is an understudied contributor to prehospital delay. We aimed to explore decision delay as a component of prehospital delay. For this correlational study, 170 Thai acute stroke patients were interviewed to explore their treatment-seeking decision factors: prior stroke knowledge, onset context, and cognitive, emotional, and behavioral factors. Participants’ mean age was 61.2 years, and 46% were women. Median decision delay and prehospital delay times were 120 and 372 minutes. Decision delay represented 49% of prehospital delays. Factors shortening decision delay were atrial fibrillation, prior stroke knowledge, perceived cause of symptoms as stroke, perceived severity of symptoms, and advice from bystanders to seek treatment. In contrast, seeking support from others and self-treatment affected prolonged decision delay. Shortening decision delay, often under the patient or bystander control, can reduce overall prehospital delay.
Physiologically‐Based Pharmacokinetic Modeling‐Guided Dose Management of Oral Anticoagulants when Initiating Nirmatrelvir/Ritonavir (Paxlovid) for COVID‐19 Treatment

Patients with coronavirus disease 2019 (COVID‐19) with cardiovascular diseases who are at higher risk of progressing to critical illness should be treated with nirmatrelvir/ritonavir (Paxlovid). Ritonavir, the booster in nirmatrelvir/ritonavir, modulates multiple drug metabolizing enzymes and transporters, complicating its use in real‐world clinics. We aimed to apply physiologically‐based pharmacokinetic (PBPK) modeling to simulate the complex drug–drug interactions (DDIs) of ritonavir with two anticoagulants, rivaroxaban and racemic warfarin, to address this important clinical conundrum. Simulations were implemented within Simcyp Simulator. Compound and population models were adopted from Simcyp and our previous studies. Upon verification and validation of the PBPK model of ritonavir, prospective DDI simulations with the anticoagulants were performed in both the general population (20–65 years) and geriatric subjects (65–85 years) with or without moderate renal impairment. Elevated rivaroxaban concentrations were simulated with nirmatrelvir/ritonavir treatment, where the impact was more profound among geriatric subjects with renal impairment. The overexposure of rivaroxaban was restored to normal range on day 4 post‐discontinuation of nirmatrelvir/ritonavir, corroborating with the recovery of enzyme activity. A lower 10 mg daily dose of rivaroxaban could effectively maintain acceptable systemic exposure of rivaroxaban during nirmatrelvir/ritonavir treatment. Treatment of ritonavir marginally declined simulated S‐warfarin concentrations, but substantially elevated that of R‐warfarin, resulting in a decrease in the international normalized ratio (INR). As INR only recovered 2 weeks post‐nirmatrelvir/ritonavir treatment, a longer surveillance INR for warfarin becomes important. Our PBPK‐guided simulations evaluated clinically important yet untested DDIs and supports clinical studies to ensure proper anticoagulation management of patients with COVID‐19 with chronic coagulative abnormalities when initiating nirmatrelvir/ritonavir therapy.
Blinatumomab is associated with favorable outcomes in patients with B‐cell lineage acute lymphoblastic leukemia and positive measurable residual disease at a threshold of 10−4 and higher

The presence of measurable residual disease (MRD) is the strongest predictor of relapse in acute lymphoblastic leukemia (ALL). We conducted a prospective, single‐arm, phase II study in adults with B‐cell ALL with MRD ≥1 × 10−4 after ≥3 months from the start of frontline therapy or one month from any salvage therapy. Blinatumomab was administered at a standard dosing of 28 micrograms daily as a continuous infusion for up to five cycles and up to four additional maintenance cycles. Thirty‐seven patients with a median age of 43 years (range, 22–84 years) were treated. Twenty‐seven patients (73%) were treated in first complete remission (CR) and 10 patients (27%) in second CR and beyond. Eighteen patients (49%) had Philadelphia‐chromosome positive ALL and received concomitant tyrosine kinase inhibitor therapy. Twenty‐three patients (62%) had a baseline MRD ≥10−3. A median of three cycles (range, 1–9 cycles) were administered. Overall, 27 patients (73%) achieved MRD‐negative remission. With a median follow‐up of 31 months (range, 5–70 months), the estimated 3‐year relapse‐free survival (RFS) rate was 63% (95% confidence interval [CI], 43%–77%) and overall survival (OS) rate 67% (95% CI, 46%–81%). These rates were 51% (95% CI, 27%–70%) and 61% (95% CI, 36%–78%) in patients with baseline MRD ≥1 × 10−3, and 83% (95% CI, 45%–95%) and 77% (95% CI, 32%–95%) in patients with baseline MRD <10−3 respectively. The rates of adverse events were consistent with previous studies of blinatumomab. In summary, blinatumomab induced MRD negativity in most patients and resulted in high rates of RFS and OS. This study is registered at www.clinicaltrials. gov as #NCT02458014. Funding was provided by Amgen Inc.
Hidden in plain sight: novel molecular data reveal unexpected genetic diversity among paramphistome parasites (Digenea: Paramphistomoidea) of European water frogs

Abstract Abstract Parasites might represent a helpful tool in understanding the historical dispersion and phylogeography of their hosts. In order to reveal whether the migration routes and diversification of hosts can be traceable in the genetic structures of their parasites, we investigated the diversity of paramphistomoid trematodes of Pelophylax frogs in 2 geographically distant European regions. Water frogs belonging to the genus Pelophylax represent a striking example of a species with a high variety of ecological adaptations and a rich evolutionary history. The parasites were collected from 2 Balkan endemic species, P. epeiroticus and P. kurtmuelleri, and 2 species in Slovakia, P. esculentus and P. ridibundus. While in Slovakia, Pelophylax frogs harboured 2 species, the diplodiscid Diplodiscus subclavatus and the cladorchiid Opisthodiscus diplodiscoides, only the former was recorded in the south-western Balkans. Remarkably high genetic diversity (16 unique mitochondrial cox1 haplotypes, recognized among 60 novel sequences) was observed in D. subclavatus, and subsequent phylogenetic analyses revealed a strong population-genetic structure associated with geographical distribution. We also evidenced the existence of 2 divergent D. subclavatus cox1 haplogroups in the south-western Balkans, which might be associated with the historical diversification of endemic water frogs in the regional glacial microrefugia.
Financial Toxicity Intervention Improves Outcomes in Patients With Hematologic Malignancy

PURPOSE: Patients with hematologic malignancies are extremely vulnerable to financial toxicity (FT) because of the high costs of treatment and health care utilization. This pilot study identified patients at high risk because of FT and attempted to improve clinical outcomes with comprehensive intervention. METHODS: All patients who presented to the Levine Cancer Institute's Leukemia Clinic between May 26, 2019, and March 10, 2020, were screened for inclusion by standardized two question previsit survey. Patients screening positive were enrolled in the comprehensive intervention that used nurse navigators, clinical pharmacists, and community pro bono financial planners. Primary outcomes were defined as improvement in mental and physical quality of life in all patients and improvement in overall survival in the high-risk disease group. RESULTS: One hundred seven patients completed comprehensive intervention. Patients experiencing FT had increased rates of noncompliance including to prescription (16.8%) and over-the-counter medications (15.9%). The intervention resulted in statistically significantly higher quality of life when measured by using Patient-Reported Outcomes Measurement Information System physical (12.5 ± 2.2 v 13.7 ± 1.8) and mental health scores (11.4 ± 2.2 v 12.4 ± 2.2; all P < .001). In patients with high-risk disease (as determined by using disease-specific scoring systems), risk of death in those receiving the intervention was 0.44 times the risk of death in those without the intervention after adjusting for race, and treatment with stem-cell transplant, oral chemotherapy, or immunotherapy (95% CI, 0.21 to 0.94; P = .034). CONCLUSION: Screening and intervention on FT for patients with hematologic malignancies is associated with increased quality of life and survival.
Reduced anhedonia following internet-based cognitive-behavioral therapy for depression is mediated by enhanced reward circuit activation

Abstract Background Major depressive disorder (MDD) is a highly prevalent psychiatric condition, yet many patients do not receive adequate treatment. Novel and highly scalable interventions such as internet-based cognitive-behavioral-therapy (iCBT) may help to address this treatment gap. Anhedonia, a hallmark symptom of MDD that refers to diminished interest and ability to experience pleasure, has been associated with reduced reactivity in a neural reward circuit that includes medial prefrontal and striatal brain regions. Whether iCBT can reduce anhedonia severity in MDD patients, and whether these therapeutic effects are accompanied by enhanced reward circuit reactivity has yet to be examined. Methods Fifty-two MDD patients were randomly assigned to either 10-week iCBT (n = 26) or monitored attention control (MAC, n = 26) programs. All patients completed pre- and post-treatment assessments of anhedonia (Snaith–Hamilton Pleasure Scale; SHAPS) and reward circuit reactivity [monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI)]. Healthy control participants (n = 42) also underwent two fMRI scans while completing the MID task 10 weeks apart. Results Both iCBT and MAC groups exhibited a reduction in anhedonia severity post-treatment. Nevertheless, only the iCBT group exhibited enhanced nucleus accumbens (Nacc) and subgenual anterior cingulate cortex (sgACC) activation and functional connectivity from pre- to post-treatment in response to reward feedback. Enhanced Nacc and sgACC activations were associated with reduced anhedonia severity following iCBT treatment, with enhanced Nacc activation also mediating the reduction in anhedonia severity post-treatment. Conclusions These findings suggest that increased reward circuit reactivity may contribute to a reduction in anhedonia severity following iCBT treatment for depression.
Risk Stratification for Pregnancies Diagnosed With Fetal Growth Restriction Based on Placental MRI

Diagnosis of fetal growth restriction (FGR) entails difficulties with differentiating fetuses not fulfilling their growth potential because of pathologic conditions, such as placental insufficiency, from constitutionally small fetuses. The feasibility of placental MRI for risk stratification among pregnancies diagnosed with FGR remains unexplored.
The impact of COVID-19 lockdown on abortion care: a time series analysis of data from Marie Stopes Nepal

Abstract The COVID-19 pandemic significantly impacted sexual and reproductive health and rights. Nepal implemented a nationwide lockdown in March 2020, limiting population movement and service access. The 36 clinics run by Marie Stopes Nepal (MSN) closed for varying periods at the beginning of lockdown. This study assesses the impact of lockdown and associated clinic closures on abortion services within MSN’s network. An interrupted time-series analysis of clinic-level MSN data compared abortion service use in the pre-closure and post-reopening periods, focusing on the following outcomes: number of abortion care visits, proportion of abortion-related visits, gestational age at time of abortion care and demographics of patients accessing abortion care. Subsequent meta-analyses combined clinic-level results to generate outcome-specific pooled effect estimates. As MSN clinics reopened, during ongoing wider lockdown, weekly visits for abortion care decreased by 37% on average, but abortion increased as a proportion of services post-reopening (OR: 1.53) compared with pre-closure, with no evidence of a change in the proportion of higher gestation abortions. The demographic profile of abortion care clients was altered, with post-reopening clients more likely to have completed primary education (OR: 1.54) and be aged 25 years or older (OR: 1.31) compared with pre-closure clients. COVID-19 lockdown and associated clinic closures reduced the absolute number of abortion services provided within MSN’s network, impacting the composition of service provision. Reductions in safe abortion and wider SRH access will have wide-ranging consequences, curtailing crucial reproductive rights. Policy-makers must ensure ongoing abortion access to protect rights and ensure access.
Pharmacokinetics of Oral Nirmatrelvir/Ritonavir, a Protease Inhibitor for Treatment of COVID‐19, in Subjects With Renal Impairment

Nirmatrelvir coadministered with ritonavir is highly efficacious in reducing the risk of coronavirus disease 2019 (COVID‐19) adverse outcomes among patients at increased risk of progression to severe disease, including patients with chronic kidney disease. Because nirmatrelvir is eliminated by the kidneys when given with ritonavir, this phase I study evaluated the effects of renal impairment on pharmacokinetics, safety, and tolerability of nirmatrelvir/ritonavir. Participants with normal renal function (n = 10) or mild, moderate, or severe renal impairment (n = 8 each) were administered a single 100‐mg nirmatrelvir dose with 100 mg ritonavir given 12 hours before, together with and 12 and 24 hours after the nirmatrelvir dose. Systemic nirmatrelvir exposure increased with increasing renal impairment, with mild, moderate, and severe renal impairment groups having respective adjusted geometric mean ratio areas under the plasma concentration‐time profile from time 0 extrapolated to infinite time of 124%, 187%, and 304% vs. the normal renal function group. Corresponding ratios for maximum plasma concentration were 130%, 138%, and 148%. Apparent clearance was positively correlated with estimated glomerular filtration rate, and geometric mean renal clearance values were particularly lower for the moderate (47% decrease) and severe (80% decrease) renal impairment groups vs. the normal renal function group. Nirmatrelvir/ritonavir exhibited an acceptable safety profile; treatment‐related adverse events were mild in severity, and there were no significant findings regarding laboratory measurements, vital signs, or electrocardiogram assessments. These findings led to a dose reduction recommendation for nirmatrelvir/ritonavir in patients with moderate renal impairment (150/100 mg nirmatrelvir/ritonavir instead of 300/100 mg twice daily for 5 days). NCT04909853.
COVID-19 cases among medical laboratory services staff in South Africa, 2020–2021: A cohort study

Medical laboratory workers may have an increased risk of COVID-19 due to their interaction with biological samples received for testing and contamination of documents. Records of COVID-19 laboratory-confirmed positive cases within the medical laboratory service were routinely collected in the company’s Occupational Health and Safety Information System (OHASIS). Surveillance data from the OHASIS system were extracted from 1 April 2020 to 31 March 2021. An epidemic curve was plotted and compared to that for the country, along with prevalence proportions and incidence rates. The odds of COVID-19 infection were categorised by job and compared to the US Occupational Risk Scores. A logistic regression model assessed the risk of COVID-19 infection per occupational group. A total of 2091 (26% of staff) COVID-19 positive cases were reported. The number of COVID-19 cases was higher in the first wave at 46% (967/2091) of cases, than in the second wave 40% (846/2091) of cases. There was no significant difference in COVID-19 prevalence between male and female employees. The job categories with the most increased risk were laboratory managers [AOR 3.2 (95%CI 1.9–5.1)] and laboratory support clerks [AOR 3.2 (95%CI 1.9–5.2)]. Our study confirms that some categories of medical laboratory staff are at increased risk for COVID-19; this is a complex interaction between workplace risk factors, community interaction, socioeconomic status, personal habits, and behaviour. Targeted interventions are recommended for high-risk groups. OHASIS has the potential to generate data for surveillance of health care workers and contribute towards a South African risk profile.
Highly Active Nano-Reactor for Responding Tumor Microenvironment and Antitumor Therapy

The tumor microenvironment is complex and changeable, so the design of a nano-delivery system for the tumor microenvironment has attracted wide attention. Based on this, we designed an intelligent nano-reactor for the characteristics of acidic pH and hypoxia in the tumor microenvironment. Firstly, the silver nano-balls were synthesized by the biological template method, which exhibited a good photothermal conversion efficiency and can realize the photothermal treatment of tumor sites. Subsequently, the hypoxic prodrug tirapazamine (TPZ) and polydopamine (PDA) for chemotherapy were self-assembled. After PDA arrived at the tumor site (pH 5.5) from the normal physiological environment (pH 7.4), the hypoxic prodrug TPZ was released in pH response by PDA. Subsequently, TPZ selectively induced obvious cell damage under tumor hypoxia stimulation but had no toxic effect on normal cells under normal oxygen. In addition, the nano-converter was loaded with iRGD on the surface, which enhanced the targeted delivery of the nano-reactor to achieve a highly effective antitumor effect. The nano-reactor was capable of combining photothermal/chemotherapy therapy. Importantly, it can selectively kill tumor cells without damaging normal cells based on the characteristics of the tumor microenvironment, with high bio-safety and clinical transformation potential.
Building persuasiveness into information systems

Often the purpose of personal health and well-being systems is to change users’ behaviour. Many theoretical frameworks have been developed to support the design and evaluation of these persuasive systems for behaviour change, but their design remains challenging. No systematic way yet exists by which to put the information into practice and build in persuasiveness effectively. The aim of this study is to investigate how the Persuasive Systems Design (PSD) model can be utilised so as to support the development of personal health and well-being systems. To do this, the study discusses and analyses related research and also integrates the PSD model into the development of two health-related behaviour change support systems. In Case 1, the purpose of using the PSD model was to identify new persuasive functionality within a fall risk assessment and fall prevention system. In Case 2, the purpose of using the PSD model was to identify new persuasive functionality and new service concepts within an existing smartphone application for mental wellbeing. The study shows that the PSD model has been used in the development of BCSSs to describe the overall process, analyse the persuasion context and design system qualities. It has also been applied in the evaluation of the existing systems by providing heuristics for expert evaluations and systematic ways to analyse user experience data. The study also reveals that the PSD model can be successfully applied during the user requirements analysis and concept design phases to identify new potential persuasive functionalities. In both Case 1 and 2, this resulted in having more variety in persuasive functionalities compared to those in the initial user requirements or existing application. The PSD model provides support for designing and evaluating BCSSs, but some future directions of development of the model can be recognised.