bluuebunny/crossref_metadata_2025 huggingface dataset:
The response of anti-VEGF therapy and tamoxifen withdrawal of tamoxifen-induced cystoid macular edema in the same patient
Authors: Li Chuanyu , Xiao Jun , Zou He , Yang Bo , Luo Lifu
Published: May 2021

Background

Numerous cases with ocular toxicity secondary to tamoxifen have been reported, and became more apparent with keratopathy, cataract, optic neuritis, macular holes, crystalline retinopathy with or without cystoid macular edema (CME). Withdrawing tamoxifen with the approval of the oncologist is the major treatment for cases with tamoxifen-induced retinopathy.

Case presentation

We herein reported a patient with a two-year history of painless and reduced visual acuity in both eyes who received tamoxifen therapy for 6 years. Tamoxifen-induced rentinopathy with CME showed significant development even though the patient has already discontinued tamoxifen treatment for 6 months. Anatomic improvements after intravitreal ranibizumab injection in both eyes were significant but were temporary. Surprisingly, CME in both eyes has been resolved spontaneously after 10 months in the penultimate visit without any therapy.

Conclusion

Intravitreal ranibizumab injection temporarily improved the anatomy of the eyes in a case with tamoxifen-induced CME, and only tamoxifen withdrawal can bring a sustained effect.
The functional impairment of different subtypes and occupational states in euthymic patients with bipolar disorder
Authors: Liu Xinyu , Ma Xiaojuan , Wang Wenchen , Zhang Jian , Sun Xia , Luo Xingguang , Zhang Yong
Published: May 2021

Background

The aim was to explore the associations between clinical symptoms, demographic variables, social and neurocognitive functioning in euthymic patients with bipolar disorder (BD) stratified by subgroups of DSM-IV BD (type I (BD-I) and type II (BD-II)) and occupational status (employed/unemployed), and to highlight the significance of occupational status when assessing social and neurocognitive functioning in euthymic BD patients.

Methods

A total of 81 euthymic BD patients were participated in the study. The severity of the depressive and manic/hypomanic symptoms was measured using the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Young Mania Rating Scale (YMRS), respectively. Social functioning and neurocognitive functioning were evaluated by the Functioning Assessment Short Test (FAST) and neurocognitive measures, respectively.

Results

Employed BD patients displayed greater social functioning (autonomy, occupational functioning, interpersonal relationship domain) and better verbal learning performance and speed of processing than unemployed BD patients. The correlation between neurocognitive functioning and social functioning was stronger in the employed group than in the unemployed group. There were no significant differences in neurocognitive and social functioning between the BD-I and BD-II groups, and the correlation between neurocognitive functioning and social functioning was similar between the BD-I and BD-II groups.

Conclusion

Employed BD patients may present greater occupational functioning and interpersonal relationships, as well as better verbal learning performance and speed of processing.
A new lesser metatarsophalangeal joint replacement arthroplasty design - in vitro and cadaver studies
Authors: Saragas Nikiforos P. , Ferrao Paulo N. F. , Strydom Andrew
Published: May 2021

Background

Isolated degenerative joint disease and/or Freiberg’s infraction of the lesser metatarsophalangeal joint, although not frequent may become debilitating in the younger individual. Currently, once conservative management fails, the mainstay of treatment is debridement and excision-interposition arthroplasty. Replacement arthroplasty has been ineffective in the long term as the joints are subject to severe repetitive fatigue loading over small articulating surfaces through a wide range of motion. This is an in vitro and cadaver study of a new design replacement arthroplasty developed by the senior author.

The aim of this study is to evaluate this novel replacement arthroplasty of the lesser metatarsophalangeal joint in a laboratory setting and cadaver implantation.

Methods

This three-component mobile bearing device is made of titanium and high density polyethylene which evolved over 4 years. It was subjected to 5,000,000 cycles in a laboratory under physiological and excessive forces to assess resistance to fatigue failure and wear pattern of the polyethylene liner. Following these tests, it was implanted in 15 fresh frozen cadavers at various stages of its development, during which the surgical technique was perfected. Range of motion and stability was tested using custom made instrumentation in four cadavers. The implant was inserted in a further two cadavers by an independent foot and ankle surgeon to check reproducibility.

Results

The device showed almost no signs of wear or surface deformation under physiological forces. The surgical technique was found to be simple and reproducible in the cadaver trial.

The average dorsiflexion was 28.5° and 28.9° pre- and post-implant respectively. The average plantar flexion was 33.8° and 20.8° pre- and post- implant respectively. The joints were stable both pre- and post-operatively. Post-operative stability was objectively assessed for dorsal displacement and dorsiflexion using a 5 kgf (49 N) and was found to be excellent.

Conclusion

This novel lesser metatarsophalangeal joint replacement arthroplasty has been developed as an option in the surgical treatment of symptomatic degenerative joint disease and/or Freiberg’s infraction resistant to conservative treatment. The implant was found to be durable and resistant to wear in the laboratory testing. The cadaver studies have shown it to require minimal specialized instrumentation with good surgical reproducibility.

This proof of concept study is the basis for clinical trials.
Dental practice closure during the first wave of COVID-19 and associated professional, practice and structural determinants: a multi-country survey
Authors: Abdelrahman Hams , Atteya Sara , Ihab Merna , Nyan Myat , Maharani Diah A , Rahardjo Anton , Shaath Mohammed , Aboalshamat Khalid , Butool Syeda , Shamala Anas , Baig Lubna , El Tantawi Maha
Published: May 2021

Background

The coronavirus outbreak (COVID-19) in China has influenced every aspect of life worldwide. Given the unique characteristics of the dental setting, the risk of cross-infection between dental practitioners and patients is high in the absence of adequate protective measures, and dentists may develop severe anxiety in relation to the current pandemic. The limited provision of services and widespread closure of dental practices have raised concerns among dental professionals about the financial impact. The present study assessed the frequency of dental practice closure during the pandemic’s first wave in several countries and whether closures and their associated factors differ between the private and non-private sectors.

Methods

An electronic cross-sectional survey questionnaire was sent to dentists in several countries, from April to May 2020. The survey assessed professional, practice related and country-level structural factors elucidating the reason for practice closure. Multilevel logistic regression was used to assess the association between practice closure and these factors, and differences were evaluated by sector type.

Results

Dentists from 29 countries (n = 3243) participated in this study. Most of the participants (75.9%) reported practice closure with significantly higher percentage in the private sector than the non-private sector. Greater pandemic-related fears were associated with a significantly higher likelihood of practice closure in the private (odds ratio [OR] = 1.54, 95% confidence interval [CI] 1.24, 1.92) and non-private (OR = 1.38, 95% CI 1.04, 1.82) sectors. Dentists in non-private rural areas (OR = 0.58, 95% CI 0.42, 0.81), and those in hospitals (overall OR = 0.60, 95% CI 0.36, 0.99) reported a low likelihood of closure. A high likelihood of closure was reported by dentists in the academia (OR = 2.13, 95% CI 1.23, 3.71). More hospital beds at the country-level were associated with a lower likelihood of closure in the non-private sector (OR = 0.65, 95% CI 0.46, 0.91). Private- sector dentists in high- income countries (HICs) reported fewer closures than those in non-HICs (OR = 0.55, 95% CI 0.15, 1.93).

Conclusions

Most dentists reported practice closure because of COVID-19, and greater impacts were reported in the private sector than in the non-private sector. Closure was associated with professional, practice, and country-levels factors.
A systematic review of the use of virtual reality or dental smartphone applications as interventions for management of paediatric dental anxiety
Authors: Cunningham Andrea , McPolin Orlagh , Fallis Richard , Coyle Catherine , Best Paul , McKenna Gerald
Published: May 2021

Background

Virtual reality (VR) has been used successfully in medicine both as a distraction tool during procedures, and as an acclimatisation tool to prepare for a procedure or experience. It has not yet become widely used in dentistry, but could theoretically have a role in exposure-based acclimatisation for dental experiences.

Methods

To examine the use of VR or bespoke dental smartphone applications pre- or perioperatively in dentistry, to decrease anxiety in a paediatric population attending for dental examination or treatment, compared with children/adolescents who receive no intervention, or more conventional behavioural management techniques.

Searches were made of eight electronic databases: the Cochrane Oral Health Group’s Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE(PubMed), EMBASE, PsycINFO, CINAHL, Scopus and Web of Science. Further searches reference cross‐checks were performed to identify studies that were not discovered online.

Results

Systematic reviews and randomised control trials have demonstrated the successful use of VR to both distract patients perioperatively during medical procedures, and also preoperatively to prepare them for these interventions. However, to date, VR has only been applied to dentistry in a very limited number of studies. Three studies using virtual reality in a dental setting demonstrated decreased pain and anxiety compared with no intervention. All three of these studies were carried out in the perioperative period. A fourth study used a bespoke dental app and imagery to prepare patients with Autism Spectrum Disorder (ASD) for dental treatment, finding statistically significant decreases in both the number of appointments and number of attempts required to carry out a procedure.

Conclusion

VR is a promising tool which to date has been under-utilised in dentistry. High quality, clinical studies are required to assess the use of preoperative VR and smartphone applications to prepare patients for dental examination and procedures under local or general anaesthetic.
Streptococcus salivarius inhibits immune activation by periodontal disease pathogens
Authors: MacDonald Kyle W. , Chanyi Ryan M. , Macklaim Jean M. , Cadieux Peter A. , Reid Gregor , Burton Jeremy P.
Published: May 2021

Background

Periodontal disease represents a major health concern. The administration of beneficial microbes has been increasing in popularity over efforts to manipulate the microbes using antimicrobial agents. This study determined the ability of Streptococcus salivarius to inhibit IL-6 and IL-8 production by gingival fibroblasts when activated by periodontal pathogens and their effect on the salivary microbiome.

Methods

Primary human gingival fibroblasts were challenged with Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum and a combination of all three. IL-6 and IL-8 cytokine release were measured. Using this same model, S. salivarius K12, M18 and different supernatant and whole-cell lysate fractions of S. salivarius K12 were administered to pathogen-induced fibroblasts. A patient study of healthy participants was also conducted to determine the effect S. salivarius K12 had on the native microbiome using 16S next generation sequence analysis.

Results

All pathogens tested induced a significant IL-6 and IL-8 response. S. salivarius K12 or M18, did not exhibit an increase in inflammatory cytokines. When either of the probiotic strains were co-administered with a pathogen, there were significant reductions in both IL-6 and IL-8 release. This effect was also observed when gingival fibroblasts were pre-treated with either S. salivarius K12 or M18 and then stimulated with the oral pathogens. Chewing gum containing S. salivarius K12 did not alter the salivary microbiome and did not increase inflammatory markers in the oral cavity.

Conclusion

S. salivarius K12 and M18 prevented immune activation induced by periodontal disease pathogens. S. salivarius K12 did not alter the salivary microbiome or induce immune activation when administered as a chewing gum. These results warrant further study to determine if it may be an effective treatment in a model of periodontal disease.
A pathway to negative acculturation: marital maladjustment mediates the relationship between the length of residency and depressive symptoms in immigrant women in Taiwan
Authors: Lien Mei-Huei , Huang Sheng-Shiung , Yang Hao-Jan
Published: May 2021

Background

Immigrant women in Taiwan experience a variety of acculturative and marital problems that result in a mental-health problems. We examined the mediational effect of marital adjustment on the relationship between acculturation and depressive symptoms in immigrant women in Taiwan.

Methods

All participants (N = 127) were interviewed to collect data regarding their basic sociodemographics, depressive symptoms, acculturation (using language proficiency and years in Taiwan as indicators), and marital adjustment. We used a Sobel test to examine how marital adjustment mediates the relationship between acculturation and depressive symptoms.

Results

Our results indicated that an increased length of residency exacerbated depressive symptoms (β = 0.62, p = 0.03) and that this relationship contributed, in part, to the mediational effect of marital adjustment. That is, marital adjustment deteriorated with the length of residency (β =  − 0.26, p = 0.0013), resulting in the development of depressive symptoms (β =  − 0.95, p = 0.0013).

Conclusion

Although the duration of residency may be useful as a proxy for acculturation in the assessment of some health outcomes, our findings imply that it is better to conceptualize it as a cumulative stress when considering the mental health of immigrant women. Marital maladjustment acts as a mediator in this relationship. As such, it is important to provide immigrant families with programs and resources to assist them in adapting to their marriages and to improve the mental health of immigrant women.
Adaptation of community-based distribution of family planning services to context-specific social networks: a case of marriage counsellors in Lusaka district, Zambia
Authors: Nyundo Lucy , Whittaker Maxine , Eagle Lynne , Low David R.
Published: May 2021

Background

The significant contribution of community-based distribution (CBD) of family planning services and contraceptives to the uptake of contraceptives in hard-to-reach communities has resulted in the scaling-up of this approach in many Sub-Saharan countries. However, contextual factors need to be taken into consideration. For example, social network influence (e.g. spouse/partner, in-laws, and parents) on fertility decisions in many African and Asian societies is inevitable because of the social organisational structures. Hence the need to adapt CBD strategies to the social network context of a given society.

Methods

Data collection involved structured interviews from August 2018 to March 2019. Randomly selected respondents (n = 149) were recruited from four purposively selected health facilities in Lusaka district, Zambia. Respondents were screened for age (> 15 yrs.) and marital status. A mix of categorical and qualitative data was generated. The Statistical Package for Social Sciences (SPSS®24) was used to carry out descriptive analysis and tests of association (Fisher’s exact) while Nvivo®12 was used to analyse the qualitative data using a deductive thematic approach.

Results

The results indicate that pre-marriage counselling (pre-MC) influences key elements of the husband-wife relationship (p > 0.005), namely; sexual relationship, inter-personal communication, assignation of roles and responsibilities, leadership and authority. These elements of the husband-wife relationship also affect how spouses/partners interact when making fertility decisions. More importantly, the majority (86%) of the respondents indicated having a continuing relationship with their marriage counsellors because of the need to consult them on marital issues.

Conclusion

Marriage counsellors, though hardly reported in fertility studies, are important ‘constituents’ of the social network in the Zambian society. This is because marriage counsellors are trusted sources of information about marital issues and often consulted about family planning but perceived not to have the correct information about modern contraceptives. In this context, pre-MC offers a readily available, sustainable and culturally appropriate platform for disseminating accurate information about modern contraceptives provided in a private and personal manner. Therefore, the CBD strategy in Zambia can harness marriage counsellors by recruiting and training them as community agents.
Text message reminders and peer education increase HIV and Syphilis testing among female sex workers: a pilot quasi-experimental study in Uganda
Authors: Muhindo Richard , Mujugira Andrew , Castelnuovo Barbara , Sewankambo Nelson K. , Parkes-Ratanshi Rosalind , Kiguli Juliet , Tumwesigye Nazarius Mbona , Nakku-Joloba Edith
Published: May 2021

Background

Globally, female sex workers (FSW) are disproportionately affected by HIV and other sexually transmitted infections (STIs). However, uptake of STI and HIV testing services among FSW in sub-Saharan Africa remains low. We aimed to assess the effect of FSW-led peer education and text message reminders on 3-monthly syphilis and HIV testing among FSW in Uganda.

Methods

Between September 2019 and February 2020, we implemented weekly peer education sessions and bi-monthly SMS reminders for FSW in Mbarara (intervention city). Peer education sessions were implemented by 20 FSW, who received five days of basic training as peer educators. We held monthly meetings with peer educators throughout the six-month implementation period. FSW in Mbale (control city) continued to receive standard of care consisting of HIV testing outreach campaigns, and facility-based testing. Using a quasi-experimental design in one intervention city, and one control city, we conducted pre- and post- questionnaire-based surveys on recent syphilis and HIV testing behavior among FSW in July-October 2018, and March 2020. We compared proportions and prevalence ratios at baseline and follow-up using chi-square tests and negative binomial regression.

Results

We conducted 436 interviews (200 before/236 after) with FSW. At baseline similar proportions reported taking an HIV test (57 % vs. 54 %;p = 0.72), and a syphilis serology test (35 % vs. 39 %;p = 0.67) in the intervention and control cities, respectively, in the prior three months. After the intervention, this proportion increased to 82 % (95 % confidence interval [CI] 74.0-88.2) for HIV, and 81 % (95 % CI: 73.0–87.0) for syphilis in the intervention city. Relative to baseline in the control city, the proportion testing for HIV was unchanged (52 %) but decreased for syphilis (26 %).

Conclusions

Bi-monthly text message reminders with weekly peer education sessions increased uptake of 3-monthly syphilis and HIV testing in a Ugandan female sex work population and could help increase sex worker engagement in HIV/STI services in line with World Health Organization recommendations.
Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte
Authors: D’Onofrio Nunzia , Scisciola Lucia , Sardu Celestino , Trotta Maria Consiglia , De Feo Marisa , Maiello Ciro , Mascolo Pasquale , De Micco Francesco , Turriziani Fabrizio , Municinò Emilia , Monetti Pasquale , Lombardi Antonio , Napolitano Maria Gaetana , Marino Federica Zito , Ronchi Andrea , Grimaldi Vincenzo , Hermenean Anca , Rizzo Maria Rosaria , Barbieri Michelangela , Franco Renato , Campobasso Carlo Pietro , Napoli Claudio , Municinò Maurizio , Paolisso Giuseppe , Balestrieri Maria Luisa , Marfella Raffaele
Published: May 2021

Rationale

About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance.

Objective

To evaluate the presence of SARS-CoV-2 in cardiomyocytes from heart autopsy of DM cases compared to Non-DM; to investigate the role of DM in SARS-COV-2 entry in cardiomyocytes.

Methods and results

We evaluated consecutive autopsy cases, deceased for COVID-19, from Italy between Apr 30, 2020 and Jan 18, 2021. We evaluated SARS-CoV-2 in cardiomyocytes, expression of ACE2 (total and glycosylated form), and transmembrane protease serine protease-2 (TMPRSS2) protein. In order to study the role of diabetes on cardiomyocyte alterations, independently of COVID-19, we investigated ACE2, glycosylated ACE2, and TMPRSS2 proteins in cardiomyocytes from DM and Non-DM explanted-hearts. Finally, to investigate the effects of DM on ACE2 protein modification, an in vitro glycation study of recombinant human ACE2 (hACE2) was performed to evaluate the effects on binding to SARS-CoV-2 Spike protein. The authors included cardiac tissue from 97 autopsies. DM was diagnosed in 37 patients (38%). Fourth-seven out of 97 autopsies (48%) had SARS-CoV-2 RNA in cardiomyocytes. Thirty out of 37 DM autopsy cases (81%) and 17 out of 60 Non-DM autopsy cases (28%) had SARS-CoV-2 RNA in cardiomyocytes. Total ACE2, glycosylated ACE2, and TMPRSS2 protein expressions were higher in cardiomyocytes from autopsied and explanted hearts of DM than Non-DM. In vitro exposure of monomeric hACE2 to 120 mM glucose for 12 days led to non-enzymatic glycation of four lysine residues in the neck domain affecting the protein oligomerization.

Conclusions

The upregulation of ACE2 expression (total and glycosylated forms) in DM cardiomyocytes, along with non-enzymatic glycation, could increase the susceptibility to COVID-19 infection in DM patients by favouring the cellular entry of SARS-CoV2.
Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study
Authors: de Ritter Rianneke , Sep Simone J. S. , van der Kallen Carla J. H. , van Greevenbroek Marleen M. J. , de Jong Marit , Vos Rimke C. , Bots Michiel L. , Reulen Jos P. H. , Houben Alfons J. H. M. , Webers Carroll A. B. , Berendschot Tos T. J. M. , Dagnelie Pieter C. , Eussen Simone J. P. M. , Schram Miranda T. , Koster Annemarie , Peters Sanne A. E. , Stehouwer Coen D. A.
Published: May 2021

Background

Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures.

Methods

In a population-based cohort study of individuals aged 40–75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders.

Results

Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: − 0.74% (− 1.22; − 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (− 3.50;4.07) and: − 0.52% (− 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation.

Conclusions

Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.
HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer
Authors: Xu Guocai , Shi Yuanyuan , Ling Xiaoting , Wang Dongyan , Liu Yunyun , Lu Huaiwu , Peng Yongpai , Zhang Bingzhong
Published: May 2021

Purpose

The role of HHLA2, a new immune checkpoint ligand, is gradually being elucidated in various solid tumours. However, its role in ovarian cancer remains unclear; thus, its expression profile and clinical significance in ovarian cancer must be examined.

Methods

We performed immunohistochemistry to examine HHLA2 expression in 64 ovarian cancer tissues and 16 normal ovarian tissues. The relationships between HHLA2 expression and clinicopathological features, prognosis, and CD8+ tumour-infiltrating lymphocytes (TILs) in patients were analysed. Additionally, the Cancer Cell Line Encyclopedia database was used to analyse the correlation between HHLA2 expression and PD-L1 or B7x expression. Furthermore, the biological function of HHLA2 in ovarian cancer cells was initially explored.

Results

Only 17.2% of ovarian cancer patients showed HHLA2 expression, which was significantly associated with the differentiation of ovarian cancer cells (p = 0.027), and well-differentiated tumours expressed higher levels of HHLA2. The density of CD8+ TIL was associated with increased HHLA2 expression (p = 0.017), and the CD8+ TIL count was higher in the HHLA2-positive group than that in the HHLA2-negative group (p = 0.023). Moreover, multivariate analysis identified HHLA2 expression as an independent prognostic factor that predicted improved survival (p = 0.049; HR = 0.156; 95% CI = 0.025–0.992). Additionally, we also found that overexpressing HHLA2 inhibited the proliferation of ovarian cancer cells.

Conclusion

HHLA2 is associated with tumour differentiation and high CD8+ TIL levels; and predicts improved survival in ovarian cancer. Along with previously reported findings that HHLA2 behaves as a co-stimulatory ligand, our study suggests that the loss of HHLA2 may contribute to the immunosuppressive microenvironment and progression of ovarian cancer.
Time-series analysis of daily ambient temperature and emergency department visits in five US cities with a comparison of exposure metrics derived from 1-km meteorology products
Authors: Thomas Nikita , Ebelt Stefanie T. , Newman Andrew J. , Scovronick Noah , D’Souza Rohan R. , Moss Shannon E. , Warren Joshua L. , Strickland Matthew J. , Darrow Lyndsey A. , Chang Howard H.
Published: May 2021

Background

Ambient temperature observations from single monitoring stations (usually located at the major international airport serving a city) are routinely used to estimate heat exposures in epidemiologic studies. This method of exposure assessment does not account for potential spatial variability in ambient temperature. In environmental health research, there is increasing interest in utilizing spatially-resolved exposure estimates to minimize exposure measurement error.

Methods

We conducted time-series analyses to investigate short-term associations between daily temperature metrics and emergency department (ED) visits for well-established heat-related morbidities in five US cities that represent different climatic regions: Atlanta, Los Angeles, Phoenix, Salt Lake City, and San Francisco. In addition to airport monitoring stations, we derived several exposure estimates for each city using a national meteorology data product (Daymet) available at 1 km spatial resolution.

Results

Across cities, we found positive associations between same-day temperature (maximum or minimum) and ED visits for heat-sensitive outcomes, including acute renal injury and fluid and electrolyte imbalance. We also found that exposure assessment methods accounting for spatial variability in temperature and at-risk population size often resulted in stronger relative risk estimates compared to the use of observations at airports. This pattern was most apparent when examining daily minimum temperature and in cities where the major airport is located further away from the urban center.

Conclusion

Epidemiologic studies based on single monitoring stations may underestimate the effect of temperature on morbidity when the station is less representative of the exposure of the at-risk population.
Health-related quality of life in Chinese population with non-alcoholic fatty liver disease: a national multicenter survey
Authors: Huang Rui , Fan Jian-Gao , Shi Jun-Ping , Mao Yi-Min , Wang Bing-Yuan , Zhao Jing-Min , Lu Lun-Gen , Zhong Bi-Hui , Zou Zheng-Sheng , Xu You-Qing , Ye Yi-Nong , Liu Long-Gen , Lin Lian-Jie , Li Jian-Ping , Rao Hui-Ying , Wei Lai
Published: May 2021

Background

Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient’s health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population.

Methods

In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL.

Results

A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330–2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001–1.011), triglyceride (HR, 1.184; 95% CI, 1.074–1.305), disease severity (HR, 3.203; 95% CI, 1.418–7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074–8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains.

Conclusions

This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.
Pediatric rheumatology in Africa: thriving amidst challenges
Authors: Migowa Angela N. , Hadef Djohra , Hamdi Wafa , Mwizerwa Oscar , Ngandeu Madeleine , Taha Yassmin , Ayodele Faleye , Webb Kate , Scott Christiaan
Published: May 2021

Background

Pediatric Rheumatology is an orphan specialty in Africa which is gradually gaining importance across the continent.

Main body

This commentary discusses the current state of affairs in the sphere of Pediatric Rheumatology across Africa and offers practical strategies to navigate the challenges encountered in research, models of care, education and training. We outline the establishment, opportunities of growth and achievements of the Pediatric Society of the African League Against Rheumatism (PAFLAR).

Conclusion

This commentary lays the foundation for establishment of a formidable framework and development of partnerships for the prosperity of Pediatric Rheumatology in Africa and beyond.
COVID-19-related stigma and its sociodemographic correlates: a comparative study
Authors: Yuan Yuan , Zhao Yan-Jie , Zhang Qing-E , Zhang Ling , Cheung Teris , Jackson Todd , Jiang Guo-Qing , Xiang Yu-Tao
Published: May 2021

Background

Coronavirus disease 2019 (COVID-19) is closely associated with physical and mental health problems; however, little is known about the severity of stigma caused by COVID-19 among its survivors. Thus, the aim of this study was to compare differences in stigma experiences of COVID-19 survivors versus healthy controls after the COVID-19 outbreak peak in China.

Methods

This cross-sectional study comprised 154 COVID-19 survivors and 194 healthy controls recruited through consecutive and convenience sampling methods, respectively. COVID-19 related stigma was measured by the Social Impact Scale (SIS). Stigma differences between the two groups were compared with analysis of covariance (ANCOVA) and a generalized linear model (GLM) was used to identify independent correlates of COVID-19-related stigma in this study.

Results

Compared with healthy controls, COVID-19 survivors reported more overall stigma (F(1,347) = 60.82,p < 0.001), and stigma in domains of social rejection (F(1,347) = 56.54,p < 0.001), financial insecurity (F(1,347) = 19.96,p < 0.001), internalized shame (F(1,347) = 71.40,p < 0.001) and social isolation (F(1,347) = 34.73,p < 0.001). Status as a COVID-19 survivor, having family members infected with COVID-19, being married, economic loss during the COVID-19 pandemic, and depressive symptoms were positively associated with higher overall stigma levels (allpvalues < 0.05).

Conclusion

COVID-19-related stigma is commonly experienced among COVID-19 survivors even though the outbreak has been well-contained in China. Routine assessment of stigma experiences should be conducted on COVID-19 survivors and appropriate psychological assistance, public education, and anti-stigma campaigns and policies should be enforced to reduce stigma within this vulnerable subpopulation.
The incidence of hydrocephalus among patients with and without spinal muscular atrophy (SMA): Results from a US electronic health records study
Authors: Viscidi Emma , Wang Nasha , Juneja Maneesh , Bhan Ishir , Prada Claudia , James Dayle , Lallier Stacie , Makepeace Corinne , Laird Karen , Eaton Susan , Dilley Anne , Hall Susan
Published: May 2021

Background

The incidence of hydrocephalus in the spinal muscular atrophy (SMA) population relative to the general population is currently unknown. Since the approval of nusinersen, an intrathecally administered drug for SMA, a small number of hydrocephalus cases among nusinersen users have been reported. Currently, the incidence of hydrocephalus in untreated SMA patients is not available, thereby making it difficult to determine if hydrocephalus is a side effect of nusinersen or part of SMA’s natural history. This retrospective, matched cohort study used electronic health records (EHRs) to estimate and compare the incidence of hydrocephalus in both SMA patients and matched non-SMA controls in the time period prior to the approval of nusinersen.

Methods

The U.S. Optum® de-identified EHR database contains records for approximately 100 million persons. The current study period spanned January 1, 2007–December 22, 2016. Patients with SMA were identified by one or more International Classification of Diseases (ICD)-9 and/or ICD-10 codes for SMA appearing as primary, admission, or discharge diagnoses, without a pregnancy diagnostic code in the 1-year time before and after the first occurrence of SMA. The first occurrence of SMA defined the index date and non-SMA controls were matched to cases. Incident cases of hydrocephalus were identified with one or more ICD-9 and/or ICD-10 code for any type of hydrocephalus following the index date. Hydrocephalus incidence rates per person-months and the incidence rate ratio comparing SMA cases with non-SMA controls were calculated.

Results

There were 5354 SMA cases and an equal number of matched non-SMA controls. Incident hydrocephalus events were identified in 42 SMA cases and 9 non-SMA controls. Hydrocephalus incidence rates per 100,000 person-months were 15.5 (95% CI: 11.2–20.9) among SMA cases and 3.3 (95% CI: 1.5–6.3) among non-SMA controls. The incidence rate ratio was 4.7 (95% CI: 2.4–10.2).

Conclusions

Based on this retrospective analysis utilizing US EHR data, SMA patients had an approximately fourfold increased risk of hydrocephalus compared with non-SMA controls in the era preceding nusinersen treatment. This study may assist in properly evaluating adverse events in nusinersen-treated SMA patients.
Policies on return and reintegration of displaced healthcare workers towards rebuilding conflict-affected health systems: a review for The Lancet-AUB Commission on Syria
Authors: Rayes Diana , Meiqari Lana , Yamout Rouham , Abbara Aula , Nuwayhid Iman , Jabbour Samer , Abouzeid Marian
Published: May 2021

Background

War and armed conflicts severely disrupt all health system components, including the healthcare workforce. Although data is limited on the scale of health care worker (HCW) displacement in conflict zones, it is widely acknowledged that conflict conditions result in the displacement of a significant portion of qualified HCWs from their country of origin. While voluntary HCW return is integral to health system rebuilding in conflict-affected and post-conflict settings, there has been little exploration of the nature of national or international policies which encourage HCW return and reintegration to their home countries in the post-conflict period.

Methods

We conducted a systematic review to identify policies and policy recommendations intended to facilitate the return of displaced HCWs to their home countries and acknowledge their contribution to rebuilding the post-conflict health system. We searched three bibliographic databases and a range of organisational and national health agency websites to identify peer-reviewed articles and grey literature published in English or Arabic between 1 January 1990 to 24 January 2021, and extracted relevant information. We classified policies and policy recommendations using an adapted version of the UNHCR 4Rs Framework.

Results

We identified nine peer-review articles and four grey literature reports that fit our inclusion criteria, all of which were published in English. These covered issues of repatriation (n = 3), reintegration (n = 2), health system rehabilitation and reconstruction (n = 2); six documents covered several of these themes. Information was available for nine conflict contexts: Afghanistan, Iraq, Kosovo, Lebanon, Namibia, Northern Uganda, South Sudan, Timor Leste, and Zimbabwe. Findings demonstrate that health system rebuilding and rehabilitation serve as precursors and reinforcers of the successful return, repatriation, and reintegration of displaced HCWs.

Conclusions

Despite the significant numbers of HCWs displaced by conflict, this study identified few specific policies and limited information explicitly focused on the repatriation and reintegration of such workers to their home country in the post-conflict period. Additional research is needed to understand the particular barriers faced by conflict-displaced HCWs in returning to their home country. Conflict-affected and post-conflict states should develop policies and initiatives that address factors within and beyond the health sector to encourage displaced HCW return and provide sustainable reintegration solutions for those who return to post-conflict health systems.
Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis
Authors: Magota Hirotoshi , Sasaki Masanori , Kataoka-Sasaki Yuko , Oka Shinichi , Ukai Ryo , Kiyose Ryo , Onodera Rie , Kocsis Jeffery D. , Honmou Osamu
Published: May 2021

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative fatal disorder in which motor neurons within the brain and spinal cord degenerate. A single infusion of mesenchymal stem cells (MSCs) delays disease progression by protecting motor neurons and restoring the blood-spinal cord barrier in the SOD1G93A transgenic ALS rat model. However, the therapeutic effect of a single infusion of MSCs is transient and does not block disease progression. In this study, we demonstrated that repeated administration of MSCs (weekly, four times) increased the survival period, protected motor functions, and reduced deterioration of locomotor activity compared to a single infusion and vehicle infusion, after which rats displayed progressive deterioration of hind limb function. We also compared the days until gait ability was lost in rats and found that the repeated-infused group maintained gait ability compared to the single-infusion and vehicle-infusion groups. These results suggest that repeated administration of MSCs may prevent the deterioration of motor function and extend the lifespan in ALS.
ROC1 promotes the malignant progression of bladder cancer by regulating p-IκBα/NF-κB signaling
Authors: Wu Qi , Zhou Xiaoqing , Li Peng , Ding Mao , You Shengjie , Xu Zhaoyu , Ye Junjie , Chen Xuedong , Tan Mingyue , Wang Jun , Wang Wei , Qiu Jianxin
Published: May 2021

Background

Regulator of cullins 1 (ROC1) is an important catalytic subunit of cullin–RING E3 ligase. Nuclear factor-kappa B (NF-κB) signaling is closely related to tumor invasion and metastasis. Earlier, we reported that ROC1 was associated with a poor prognosis in patients with bladder cancer (BCa). However, it is unclear whether ROC1 is involved in the NF-κB signaling associated with malignant BCa progression.

Methods

The expression of ROC1 and p65 in bladder cancer and paracancerous tissues were detected by immunohistochemistry (IHC). Pearson correlation was used to assess correlation between ROC1 and p65 protein expressions. The wound-healing and transwell assays were used to monitor cell invasion and migration. The effect of ROC1 on the expression of key proteins in the NF-κB signaling was determined by immunofluorescence and western blot (WB). Cycloheximide (CHX), MG132 and immunoprecipitation assays were used to evaluate the effect of ROC1 on the ubiquitination of phosphorylated inhibitor of kappa B alpha (p-IκBα). A lung metastasis mouse model was generated to detect the role of ROC1 in tumor metastasis.

Results

We found that ROC1 was up-regulated in BCa tissues and cell lines, and high ROC1 levels were positively correlated with higher tumour grade, lymph node metastasis, distant metastasis and poor prognosis. Linear-regression analysis showed significant a Pearson correlation between ROC1 and nuclear p65 expression in BCa tissue microarray (TMA) samples. Functional studies demonstrated that ROC1 promoted BCa cell invasion and migration. In vitro and in vivo experiments showed that ROC1 activated NF-κB signaling by enhancing the ubiquitination of p-IκBα, which caused p65 nuclear translocation and promoted the transcription of some metastasis-related target genes, such as urokinase-type plasminogen activator receptor (uPAR), intracellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and matrix metalloproteinase 9 (MMP9), resulting in promoting BCa metastasis.

Conclusion

ROC1 plays an important role in the progression of BCa and serves as a potential diagnostic and therapeutic target for patients with BCa.
Promoter G-quadruplex folding precedes transcription and is controlled by chromatin
Authors: Shen Jiazhen , Varshney Dhaval , Simeone Angela , Zhang Xiaoyun , Adhikari Santosh , Tannahill David , Balasubramanian Shankar
Published: May 2021

Background

Four-stranded G-quadruplexes (G4s) are DNA secondary structures in the human genome that are primarily found in active promoters associated with elevated transcription. Here, we explore the relationship between the folding of promoter G4s, transcription and chromatin state.

Results

Transcriptional inhibition by DRB or by triptolide reveals that promoter G4 formation, as assessed by G4 ChIP-seq, does not depend on transcriptional activity. We then show that chromatin compaction can lead to loss of promoter G4s and is accompanied by a corresponding loss of RNA polymerase II (Pol II), thus establishing a link between G4 formation and chromatin accessibility. Furthermore, pre-treatment of cells with a G4-stabilising ligand mitigates the loss of Pol II at promoters induced by chromatin compaction.

Conclusions

Overall, our findings show that G4 folding is coupled to the establishment of accessible chromatin and does not require active transcription.
scSNV: accurate dscRNA-seq SNV co-expression analysis using duplicate tag collapsing
Authors: Wilson Gavin W. , Derouet Mathieu , Darling Gail E. , Yeung Jonathan C.
Published: May 2021

Identifying single nucleotide variants has become common practice for droplet-based single-cell RNA-seq experiments; however, presently, a pipeline does not exist to maximize variant calling accuracy. Furthermore, molecular duplicates generated in these experiments have not been utilized to optimally detect variant co-expression. Herein, we introduce scSNV designed from the ground up to “collapse” molecular duplicates and accurately identify variants and their co-expression. We demonstrate that scSNV is fast, with a reduced false-positive variant call rate, and enables the co-detection of genetic variants and A>G RNA edits across twenty-two samples.