bluuebunny/crossref_metadata_2025_split huggingface dataset:
Japanese primary care physicians’ experience in treating their family members: a cross-sectional study
Authors: Matsunaga Taku , Kaneko Makoto , Fetters Michael D. , Inoue Machiko 
Published: September 2022

AbstractBackgroundGuidelines worldwide recommend that physicians should not treat their family members. However, studies in the U.S. have shown that approximately 74–83% of physicians have experience of treating family members. Primary care physicians were more likely to have such experiences than other specialists. In Japan, physicians do not have any guidelines regarding treating family members, and little is known about the experiences of primary care physicians. Therefore, we investigated the experience of treating family members or relatives among primary care physicians in Japan.MethodsThis cross-sectional study used an online questionnaire. We recruited 2,000 physicians who were members of the Japan Primary Care Association using random sampling. Data were collected from February 10 to March 10, 2021. We compare the experiences of treating family members between clinic-based doctors and hospital-based doctors using the chi-square test. We performed logistic regression analysis to adjust for gender, age, presence of a doctor in family, and physician’s geographic location (rural or not rural).ResultsA total of 466 physicians (response rate = 23.3%) completed the survey. Of the sample, 79.8% had experience of treating family members or relatives. In the univariate analysis, being a clinic-based physician was associated with experience in treating family members compared to hospital-based physicians (87.6% vs. 74.9%,p = 0.001). Multivariable analysis showed that being a clinic-based physician (odds ratio 2.30, 95% confidence interval 1.31–4.04) and age of 45–64 years (odds ratio 2.93, 95% confidence interval 1.74–4.93) were significantly related to experience treating family. Gender and geographic location were not statistically significant factors.ConclusionsA high percentage of Japanese primary care physicians, especially those who worked in clinics, reported experience treating family members or relatives. These findings will serve as basic data for future studies regarding the care of families and relatives of physicians in Japan.
Implementing personalised care planning for older people with frailty: a process evaluation of the PROSPER feasibility trial
Authors: Kime Nicky , Wright Alan , Heaven Anne , Hawkins Rebecca , Smith Jane , Cundill Bonnie , Foy Robbie , Lawton Rebecca , Farrin Amanda , Hulme Claire , Clegg Andrew 
Published: September 2022

Abstract
Background
Personalised Care Planning (PCP) is a collaborative approach used in the management of chronic conditions. Core components of PCP are shared decision making to achieve joint goal setting and action planning by the clinician and patient. We undertook a process evaluation within the PROSPER feasibility trial to understand how best to implement PCP for older people with frailty in the community.

Methods
The trial was set in two localities in England. We observed training sessions and intervention delivery at three time points during the 12-week intervention period. We interviewed delivery teams before, during and after the intervention period, as well as primary care staff. We interviewed older people who had received, declined or withdrawn from PCP. We explored training of staff delivering PCP, structures, mechanisms and resources needed for delivery, and influences on uptake. We undertook a framework approach to data analysis.

Findings
We observed thirteen training sessions and interviewed seven delivery staff, five primary care staff, and twenty older people, including seven who had declined or withdrawn from the intervention. Delivery teams successfully acquired skills and knowledge, but felt underprepared for working with people with lower levels of frailty. Timing of training was critical and ‘top-ups’ were needed. Engagement with primary care staff was tenuous. Older people with lower frailty were unclear of the intervention purpose and benefits, goal setting and action planning.

Conclusions
PCP has the potential to address the individualised needs of older people with frailty. However, training requires careful tailoring and is ideally on-going. Considerable efforts are required to integrate statutory and voluntary stakeholders, understanding the expectations and contributions of each agency from the outset. In addition, older people with frailty need time and support to adjust to new ways of thinking about their own health now and in the future so they can participate in shared decision making. These key factors will be essential when developing models of care for delivering PCP to support older people with frailty to sustain their independence and quality of life.

Trial registration
ISRCTN 12,363,970 – 08/11/2018.
Stronger association of perceived health with socio-economic inequality during COVID-19 pandemic than pre-pandemic era
Authors: Yun Je-Yeon , Sim Jin-Ah , Lee Sujee , Yun Young Ho 
Published: September 2022

Abstract
Objective
The COVID-19 pandemic has changed peoples’ routine of daily living and posed major risks to global health and economy. Few studies have examined differential impacts of economic factors on health during pandemic compared to pre-pandemic. We aimed to compare the strength of associations between perceived health and socioeconomic position (household income, educational attainment, and employment) estimated before and during the pandemic.

Methods
Two waves of nationwide survey [on 2018(T1;n = 1200) and 2021(T2;n = 1000)] were done for 2200 community adults. A balanced distribution of confounders (demographics and socioeconomic position) were achieved across the T2 and T1 by use of the inverse probability of treatment weighting. Distributions of perceived health [= (excellent or very good)/(bad, fair, or good)] for physical-mental-social-spiritual subdomains were compared between T1 and T2. Odds of bad/fair/good health for demographics and socioeconomic position were obtained by univariate logistic regression. Adjusted odds (aOR) of bad/fair/good health in lower household income(< 3000 U.S. dollars/month) were retrieved using the multiple hierarchical logistic regression models of T1 and T2.

Results
Perceived health of excellent/very good at T2 was higher than T1 for physical(T1 = 36.05%, T2 = 39.13%; P = 0.04), but were lower for mental(T1 = 38.71%, T2 = 35.17%; P = 0.01) and social(T1 = 42.48%, T2 = 35.17%; P < 0.001) subdomains. Odds of bad/fair/good health were significantly increased at T2 than T1 for household income (physical-mental-social; all Ps < 0.001) and educational attainment (social; P = 0.04) but not for employment (all Ps > 0.05). AORs of bad/fair/good health in lower household income were stronger in T2 than T1, for mental [aOR (95% CI) = 2.15(1.68–2.77) in T2, 1.33(1.06–1.68) in T1; aOR difference = 0.82(P < 0.001)], physical [aOR (95% CI) = 2.64(2.05–3.41) in T2, 1.50(1.18–1.90) in T1; aOR difference = 1.14(P < 0.001)] and social [aOR (95% CI) = 2.15(1.68–2.77) in T2, 1.33(1.06–1.68) in T1; aOR difference = 0.35(P = 0.049)] subdomains.

Conclusions
Risks of perceived health worsening for mental and social subdomains in people with lower monthly household income or lower educational attainment became stronger during the COVID-19 pandemic compared to pre-pandemic era. In consideration of the prolonged pandemic as of mid-2022, policies aiming not only to sustain the monthly household income and compulsory education but also to actively enhance the perceived mental-social health status have to be executed and maintained.
Associations between sexual identity, living with disability, bully victimisation, and HIV status and intimate partner violence among residents in Nigeria
Authors: Folayan Morenike Oluwatoyin , Oloniniyi Ibidunni Olapeju , Nwakamma Ikenna , Stevens-Murphy Erva-Jean , Undelikwo Gabriel , Lusher Joanne 
Published: September 2022

Abstract
Background
The aim of the study was to determine the associations between sexual identity, disability and HIV status and bullying victimisation, and a history of physical, emotional and sexual violence in Nigeria.

Methods
This was a secondary analysis of a primary dataset generated through an online survey conducted between February 7 and 19, 2021. The 3197 participants for the primary study were recruited through snowballing. The dependent variables were physical, emotional and sexual violence. The independent variables were sexual identity (heterosexual and sexual minority), HIV status (negative, positive and unknown), bullying victimisation (yes/no) and living with disability (yes/no). A multivariate logistic regression model was developed for each form of IPV. Each model was adjusted for age, sex assigned at birth, marital status and education level.

Results
Respondents living with HIV had higher odds for physical (AOR: 2.01; 95% CI: 1.46–2.76; p < 0.001), sexual (AOR: 2.17; 95%CI: 1.55–3.05; p < 0.001), and emotional (AOR: 1.59; 95%CI: 1.24–2.06; p < 0.001) violence. Also, those with history of bullying victimisation had higher odds for physical (AOR: 3.79; 95%CI: 2.86 – 5.68; p < 0.001), sexual (AOR: 3.05; 95%CI: 2.27 – 4.10; p < 0.001) and emotional (AOR: 2.66; 95%CI: 2.10 – 3.37; p < 0.001) violence. In addition, females had higher odds of physical (AOR: 1.52; 95%CI: 1.13–2.043; p < 0.001) and sexual (AOR: 1.83; 95%CI: 1.34 – 2.50; p < 0.001) violence; and respondents cohabiting (AOR: 1.95; 95%CI: 1.12 – 3.28; p = 0.012) had higher odds for emotional violence. Respondents who were married have significantly lower odds of experiencing physical (AOR: 0.66; 95%CI: 0.45 – 9.60; p = 0.029), sexual (AOR: 0.40; 95%CI: 0.26 – 0.62; p < 0.001) and emotional (AOR: 0.68; 95%CI: 0.50 – 0.93; p = 0.015) violence when compared to singles. Younger respondents also had lower odds of experiencing sexual violence (AOR: 0.97; 95%CI: 0.95–0.99; p = 0.016).

Conclusion
HIV positive status and bullying victimisation seem to increase the risk for all forms of IPV while the experience of IPV did not differ by sexual identity and disability status. The associations between age, sex, marital status and IPV may suggest moderating roles of the factors taking cognisance of the cultural context of these relationships. Future relational analysis is necessary to further understand the pathways for the associations found between the variables in this study.
Risk of diaphragmatic hernia in patients with spontaneous pneumothorax
Authors: Chen Jian-Xun , Hsu Shao-Yun , Lin Mei-Chen , Shih Pin-Keng 
Published: September 2022

Abstract
Background
Few studies have implied the incidence of diaphragmatic hernia (DH) after spontaneous pneumothorax (SP) with unknown mechanisms. The current study aimed to identify whether there is an association between the DH and SP.

Methods
We selected 46,897 patients with SP (SP cohort) and 46,897 without SP (non-SP matched cohort) from the National Health Insurance Database. Patients were frequency matched according to age, sex, and index year. The incidence of DH and its association with SP were assessed after stratifying different characteristics and comorbidities. Statistical analysis including chi-square test, t-test, cox proportional hazard model, and Kaplan–Meier method were used.

Results
The results suggested there were significant associations between SP and DH, especially in the subgroup of patients with older age (aged 40–64 years: 2.61-fold in adjusted hazard ratio (aHR), 95% confidence interval (CI): 1.27–5.36; aged > 65 years: 1.97-fold in aHR, 95% CI 1.43–2.71), male sex (2.11-fold in aHR, 95% CI 1.56–2.85), hypertension (2.05-fold in aHR, 95% CI 1.30–3.23), diabetes mellitus (2.58-fold in aHR, 95% CI 1.37–4.86), and smoking-related disease (1.86-fold in aHR, 95% CI 1.28–2.71). The SP cohort has significantly correlated with DH within 5-year follow-up (< 2 years: 3.22-fold in aHR, 95% CI 2.10–4.94; 2–5 years: 1.70-fold in aHR, 95% CI 1.05–2.75).

Conclusions
The SP cohort had a higher incidence of DH than the non-SP matched cohort. A prospective study of indications based on the findings of the current research should be performed.
Effects of different doses of methylprednisolone therapy on acute respiratory distress syndrome: results from animal and clinical studies
Authors: Hong Shukun , Jian Chao , Wang Hongye , Wang Xincheng , Xing Luchuan , Qiao Lujun 
Published: September 2022

Abstract
Background
The optimal dose of glucocorticoids for acute respiratory distress syndrome (ARDS) is uncertain. This study aimed to evaluate the effects of different doses of methylprednisolone on sepsis-induced acute lung injury (ALI) rats and a cohort of moderate and severe ARDS patients.

Methods
ALI rats, challenged with lipopolysaccharide, were randomly received intraperitoneal injection of normal saline (model group) and different doses of methylprednisolone (0.5, 2, 8 mg/kg, named as low-, moderate- and high-dose group, respectively) for 5 days. The body weight changes of rats, inflammatory factors in bronchoalveolar lavage fluid (BALF), lung wet/dry ratio, histopathological score, and the mRNA expressions of glucocorticoid receptor α (GRα), GRβ and nuclear factor-κB (NF-κB) were measured. Forty moderate and severe ARDS patients were treated with standard of care or plus different doses of methylprednisolone (40, 80, 120 mg/day, named as low-, moderate- and high-dose group, respectively) for 5 days. Clinical outcomes were PaO2/FiO2 ratio and C-reactive protein (CRP) level at day 5, intubation rate, hospital stay, 28-day mortality, and adverse events rate.

Results
In animal experiment, different doses of methylprednisolone could increase the body weight of rats, and reduce inflammatory factors in BALF and the degree of lung injury compared with model group. The efficacy of methylprednisolone at moderate-dose was better than that at low-dose, but was equivalent to that at high-dose, which was consistent with the differential changes in the mRNA expression of GRα, GRβ and NF-κB. In clinical study, the moderate-dose group was associated with higher PaO2/FiO2 ratio and lower CRP level. No significant difference in other clinical outcomes among groups was detected.

Conclusions
This study showed that the efficacy of methylprednisolone in ARDS treatment was not always dose-dependent due to the differential regulation of related receptors. The moderate-dose of methylprednisolone may be the potential optimal dose for ARDS treatment, which needs to be further verified by larger clinical trials.
Utilisation of after-hours telephone support in a home-based hospice service
Authors: Chong Poh-Heng , Lee Jasmin , Yeo Zhi-Zheng , Ang Raymond Qishun 
Published: September 2022

Abstract
Background
After-hours support from hospice providers is instrumental to patients with serious illness who choose to remain at home, particularly at end of life. Utilisation of out-of-hours support has been much characterised in terms of frequency and nature of calls, but more needs to be known to inform service customisation and resource allocation to optimise care. To this end, we stratify reasons for using the after-hours helpline according to time sensitivity, and to explore disease and person factors associated with urgent calls.

Method
Electronic medical records for incoming calls from external parties outside workhours within a large home hospice in Singapore were analysed inductively, to identify patterns and associations along study objectives. Individual code books for caller type and call reasons were created and tested in vivo, and later administered to extracted data. Patients that accessed the helpline were tracked for different outcomes, including hospital admissions and on-call home visits. Logistic regression modelling was performed to categorise call reasons by urgency and to identify disease and person factors associated with time sensitive calls.

Results
More than 5,000 calls to the helpline were made over a two-year period (2019-2020), predominantly by family caregivers (88.4%). These were in relation to 2,303 unique patients (38.9% of total patients served). After-hours calls were made an average of 2.3 times by patients across various lengths of service. Only 11.9% of calls were deemed time sensitive or urgent, requiring home visits by on-call staff (4%) or resulting in admission to hospital (7.9%). The majority were managed by primary care teams on the next workday (65.1%) and the remainder sorted during the after-hours call itself (22.3%). Call reasons or presenting issues were classified into two groups according to urgency. Calls in the year 2020, from the younger patient, preferred place of death outside the home, and caller types other than patient or healthcare worker were significantly associated with urgent calls.

Conclusion
Deeper characterisation of after-hours calls offers possibilities: service redesign for optimal resourcing and customised training for better care. Ultimately, planners, providers, and patients all stand to benefit.
Coding mechanisms for diagnosis timing in the International Classification of Diseases, Version 11
Authors: Sundararajan Vijaya , Le Pogam Marie-Annick , Southern Danielle A. , Pincus Harold Alan , Ghali William A. 
Published: September 2022

Abstract
Background
Diagnoses that arise after admission are of interest because they can represent complications of health care, acute conditions arising de novo, or acute decompensation of a chronic comorbidity occurring during the hospital stay. Three countries in the world have adopted diagnosis timing codes for a number of years. Their experience demonstrates the feasibility and utility of associating an International Classification of Diseases, Version 9 or International Classification of Diseases, Version 10 diagnostic code with information on diagnosis timing, either as part of a diagnostic field or as a separate field. However, diagnosis timing is not an integrated feature of these two classifications as it will be for International Classification of Diseases, Version 11.

Methods
We examine the different types of diagnosis timing that can be used to describe complex patients and present examples of how the new International Classification of Diseases, Version 11 codes may be used.

Results
Extension codes are one of the important new features of International Classification of Diseases, Version 11 and allow more specificity in diagnosis timing.

Conclusion
Imbedded and standardized diagnosis timing information is possible within the International Classification of Diseases, Version 11 classification system.
Macrophage Notch1 inhibits TAK1 function and RIPK3-mediated hepatocyte necroptosis through activation of β-catenin signaling in liver ischemia and reperfusion injury
Authors: Xu Dongwei , Qu Xiaoye , Tian Yizhu , Jie Zhao , Xi Zhifeng , Xue Feng , Ma Xueyun , Zhu Jianjun , Xia Qiang 
Published: September 2022

Abstract
Background
Notch signaling is highly conserved and critically involved in cell differentiation, immunity, and survival. Activation of the Notch pathway modulates immune cell functions during the inflammatory response. However, it remains unknown whether and how the macrophage Notch1 may control the innate immune signaling TAK1, and RIPK3-mediated hepatocyte necroptosis in liver ischemia and reperfusion injury (IRI). This study investigated the molecular mechanisms of macrophage Notch1 in modulating TAK1-mediated innate immune responses and RIPK3 functions in liver IRI.

Methods
Myeloid-specific Notch1 knockout (Notch1M−KO) and floxed Notch1 (Notch1FL/FL) mice (n = 6/group) were subjected to 90 min partial liver warm ischemia followed by 6 h of reperfusion. In a parallel in vitro study, bone marrow-derived macrophages (BMMs) were isolated from these conditional knockout mice and transfected with CRISPR/Cas9-mediated β-catenin knockout (KO) vector followed by LPS (100 ng/ml) stimulation.

Results
IR stress-induced Notch1 activation evidenced by increased nuclear Notch intracellular domain (NICD) expression in liver macrophages. Myeloid Notch1 deficiency exacerbated IR-induced liver damage, with increased serum ALT levels, macrophage/neutrophil accumulation, and proinflammatory cytokines/chemokines production compared to the Notch1FL/FL controls. Unlike in the Notch1FL/FL controls, Notch1M−KO enhanced TRAF6, TAK1, NF-κB, RIPK3, and MLKL but reduced β-catenin activation in ischemic livers. However, adoptive transfer of lentivirus β-catenin-modified macrophages markedly improved liver function with reduced TRAF6, p-TAK1, RIPK3 and p-MLKL in IR-challenged livers. Moreover, disruption of RIPK3 in Notch1M−KO mice with an in vivo mannose-mediated RIPK3 siRNA delivery system diminished IR-triggered hepatocyte death. In vitro studies showed that macrophage NICD and β-catenin co-localized in the nucleus, whereby β-catenin interacted with NICD in response to LPS stimulation. Disruption of β-catenin with a CRISPR/Cas9-mediated β-catenin KO in Notch1FL/FL macrophage augmented TRAF6 activation leading to enhanced TAK1 function. While CRISPR/Cas9-mediated TRAF6 KO in Notch1M−KO macrophage inhibited RIPK3-mediated hepatocyte necroptosis after co-culture with primary hepatocytes.

Conclusions
Macrophage Notch1 controls TAK1-mediated innate immune responses and RIPK3-mediated hepatocyte necroptosis through activation of β-catenin. β-catenin is required for the macrophage Notch1-mediated immune regulation in liver IRI. Our findings demonstrate that the macrophage Notch1-β-catenin axis is a crucial regulatory mechanism in IR-triggered liver inflammation and provide novel therapeutic potential in organ IRI and transplant recipients.
Replication-competent HIV-1 in human alveolar macrophages and monocytes despite nucleotide pools with elevated dUTP
Authors: Cui Junru , Meshesha Mesfin , Churgulia Natela , Merlo Christian , Fuchs Edward , Breakey Jennifer , Jones Joyce , Stivers James T. 
Published: September 2022

AbstractBackgroundAlthough CD4+memory T cells are considered the primary latent reservoir for HIV-1, replication competent HIV has been detected in tissue macrophages in both animal and human studies. During in vitro HIV infection, the depleted nucleotide pool and high dUTP levels in monocyte derived macrophages (MDM) leads to proviruses with high levels of dUMP, which has been implicated in viral restriction or reduced transcription depending on the uracil base excision repair (UBER) competence of the macrophage. Incorporated dUMP has also been detected in viral DNA from circulating monocytes (MC) and alveolar macrophages (AM) of HIV infected patients on antiretroviral therapy (ART), establishing the biological relevance of this phenotype but not the replicative capacity of dUMP-containing proviruses.ResultsAs compared to in vitro differentiated MDM, AM from normal donors had sixfold lower levels of dTTP and a sixfold increased dUTP/dTTP, indicating a highly restrictive dNTP pool for reverse transcription. Expression of uracil DNA glycosylase (UNG) was eightfold lower in AM compared to the already low levels in MDM. Accordingly, ~ 80% of HIV proviruses contained dUMP, which persisted for at least 14-days due to low UNG excision activity. Unlike MDM, AM expression levels of UNG and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) increased over 14 days post-HIV infection, while dUTP nucleotidohydrolase (DUT) expression decreased. These AM-specific effects suggest a restriction response centered on excising uracil from viral DNA copies and increasing relative dUTP levels. Despite the restrictive nucleotide pools, we detected rare replication competent HIV in AM, peripheral MC, and CD4+T cells from ART-treated donors.ConclusionsThese findings indicate that the potential integration block of incorporated dUMP is not realized during in vivo infection of AM and MC due to the near absence of UBER activity. In addition, the increased expression of UNG and SAMHD1 in AM post-infection is too slow to prevent integration. Accordingly, dUMP persists in integrated viruses, which based on in vitro studies, can lead to transcriptional silencing. This possible silencing outcome of persistent dUMP could promote viral latency until the repressive effects of viral dUMP are reversed.