bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Increasing the Overall Level or Fitting Hearing Aids on Emotional Responses to Sounds
Authors: Picou Erin M. , Rakita Lori , Buono Gabrielle H. , Moore Travis M.
Published: December 2021

Adults with hearing loss demonstrate a reduced range of emotional responses to nonspeech sounds compared to their peers with normal hearing. The purpose of this study was to evaluate two possible strategies for addressing the effects of hearing loss on emotional responses: (a) increasing overall level and (b) hearing aid use (with and without nonlinear frequency compression, NFC). Twenty-three adults (mean age  =  65.5 years) with mild-to-severe sensorineural hearing loss and 17 adults (mean age  =  56.2 years) with normal hearing participated. All adults provided ratings of valence and arousal without hearing aids in response to nonspeech sounds presented at a moderate and at a high level. Adults with hearing loss also provided ratings while using individually fitted study hearing aids with two settings (NFC-OFF or NFC-ON). Hearing loss and hearing aid use impacted ratings of valence but not arousal. Listeners with hearing loss rated pleasant sounds as less pleasant than their peers, confirming findings in the extant literature. For both groups, increasing the overall level resulted in lower ratings of valence. For listeners with hearing loss, the use of hearing aids (NFC-OFF) also resulted in lower ratings of valence but to a lesser extent than increasing the overall level. Activating NFC resulted in ratings that were similar to ratings without hearing aids (with a moderate presentation level) but did not improve ratings to match those from the listeners with normal hearing. These findings suggest that current interventions do not ameliorate the effects of hearing loss on emotional responses to sound.
An Evaluation of a Pipeline Program to Support Diversity in the Public Health Workforce: CDC Undergraduate Public Health Scholars (CUPS) Program
Authors: Young Kai Hsiang , Liburd Leandris , Penman-Aguilar Ana
Published: December 2021

Established by the Centers for Disease Control and Prevention (CDC), the goal of the CDC Undergraduate Public Health Scholars (CUPS) program is to expose students underrepresented in public health and medicine to careers in public health; ultimately, increasing the membership of these groups in these fields including biomedical sciences. CDC implemented a retrospective outcome evaluation of 1,047 students who participated in the program from 2012 to 2017. Seventy-four percent (775) of students responded to the survey that captures their academic attainment and employment status, as well as their perception of the program’s and mentors’ influence on their career path. As of 2020, 639 (83.4%) of 775 participants have enrolled in an advanced degree program, with over 80% of 639 participants pursuing degrees in biomedical sciences, public health, or health care (BSPHHC)–related fields. Two thirds (374/566) of participants who reported they had ever been employed in a career position are working/have worked in BSPHHC-related fields. Overall, 77.4% (600) of 775 participants reported either the program or the mentors, or both were extremely or very influential to their career path. Students claimed the CUPS program had “opened their eyes,” inspired their interest, cultivated their passion for the field of public health, and fueled their drive to find solutions to and in social determinants of health and contribute to health equity. The opportunity to gain work and research experience through internship placements in CUPS has “opened doors” to first jobs and advanced education and training opportunities for many students.
Investigating the Influence of Mentor–Mentee Race and Gender Pairs on Public Health Persistence
Authors: Trawick Cynthia , Monroe-White Thema , Joseph Michael , Tolbert NyThea Campbell , Tola Jigsa , Haynes John K.
Published: December 2021

Background. Mentoring and immersive experiences through internships are important means of increasing underrepresented (UR) students’ persistence in public health. However, while the positive effects of mentoring are well established, studies on the effect of race/ethnicity and gender mentor matching on persistence have produced mixed results. Aims. This article investigates the impact of homogeneous and heterogeneous mentor–mentee pairs on UR intern persistence for Project Imhotep, a summer internship program at Morehouse College. Method. The authors employ multivariable logistic regression analyses to examine the relationship between mentor and mentee race/ethnicity and gender characteristics on undergraduate intern academic persistence and career attainment. Results. Mentor demographics and institution type are predictors associated with intern academic and career persistence; however, the predictive importance of model attributes varied by outcome. Mentees paired with UR mentors (female or male) were more likely to attend graduate school, and mentees mentored by female mentors (UR female or White female) were more likely to pursue a graduate degree in public health. Finally, mentees mentored by UR females had the highest likelihood of either pursuing a graduate degree in public health or a public health career. Discussion. This article advances our understanding of how mentor–mentee race/ethnicity and gender affects the recruitment and retention of undergraduate students from racially and ethnically UR populations into public health. Conclusions. The findings suggest that the degree of shared racial/ethnic and/or gender identity between a public health intern and mentor influenced the likelihood of the intern pursuing further education or a public health career.
HIV Positive Pregnant Mothers’ Perceptions and Experiences Regarding the Prevention of Mother-to-Child Transmission, Option B+ Program
Authors: Mbatha Trusty L. , Dube Adiele
Published: December 2021

Background: eSwatini is a small population-sized sub-Sahara African country characterized by its highest human immunodeficiency virus (HIV) prevalence globally. The prevalence of HIV among pregnant women is above 40%. In the past decade, the Government of eSwatini has demonstrated a high level of commitment to virally suppress HIV spread among its population. This study explored the perceptions and experiences of HIV-positive pregnant mothers regarding the prevention of mother-to-child transmission (PMTCT) Option B+ program in order to discuss and address the gaps in the health system. Methods: Qualitative, exploratory, and descriptive research design was used. Data was collected through in-depth interviews and field notes. Data was gathered from all cases of HIV-positive pregnant mothers enrolled at a Public Health Unit. Results: Seventeen pregnant women aged between 18 and 40 years participated. Findings revealed that the Option B+ program was positively perceived as preventing HIV from mother-to-child. It boosts the immune system, deters opportunistic infections, and prolongs life. Knowledge and understanding of the program were displayed despite challenges such as discrimination and no support from families. Conclusion: PMTCT Option B+ intervention was found to be effective in reducing mother-to-child transmission of HIV. Gaps between women and men about HIV and antiretroviral therapy need to be addressed through target messaging and stigmatization discussions so that men are encouraged to disclose their HIV status. Improving access to antiretroviral and retention of women on treatment can further reduce vertical HIV infection transmission.
The Magnitude of the Health and Economic Impact of Increased Organ Donation on Patients With End-Stage Renal Disease
Authors: Chen Huey-Fen , Ali Hayatt , Marrero Wesley J. , Parikh Neehar D. , Lavieri Mariel S. , Hutton David W.
Published: December 2021

Objectives. There are several approaches such as presumed consent and compensation for deceased donor organs that could reduce the gap between supply and demand for kidneys. Our objective is to evaluate the magnitude of the economic impact of policies to increase deceased donor organ donation in the United States. Methods. We built a Markov model and simulate an open cohort of end-stage renal disease patients awaiting kidney transplantation in the United States over 20 years. Model inputs were derived from the United States Renal Data System and published literature. We evaluate the magnitude of the health and economic impact of policies to increase deceased donor kidney donation in the United States. Results. Increasing deceased kidney donation by 5% would save $4.7 billion, and gain 30,870 quality-adjusted life years over the lifetime of an open cohort of patients on dialysis on the waitlist for kidney transplantation. With an increase in donations of 25%, the cost saved was $21 billion, and 145,136 quality-adjusted life years were gained. Policies increasing deceased kidney donation by 5% could pay donor estates $8000 or incur a onetime cost of up to $4 billion and still be cost-saving. Conclusions. Increasing deceased kidney donation could significantly impact national spending and health for end-stage renal disease patients.
Shilpakar Mahasabha in Colonial Uttarakhand: Subjective Representation of Collective Self
Authors: Tamta Isha
Published: December 2021

The caste system in India got transformed as a consequence of the policies of the British Raj. The introduction of the census under the colonial government, among other things, made the most direct impact because for the first time the castes have been enumerated with great details. As a result, castes immediately not only organized themselves but also formed caste associations in order to get their status recorded in the way they thought was honourable to them. Caste associations emerged over the period to pressurize the colonial administration to improve their rank in the census. This process was especially prevalent among the lower castes in different parts of India. Shilpakar Mahashaba was a case in point in Uttarakhand. Shilpakar Mahasabha claimed new advantages from the state like reservations (quotas) in educational institutions and in the civil service. Subsequently, they also became mutual aid structures. Shilpakar Mahasabha founded schools and hostels for the children of Shilpakars and led a sort of co-operative movement. Some have argued that caste associations acted like a collective enterprise with economic, social and political objectives for their caste.
The Endoplasmic Reticulum-Mitochondria Encounter Structure and its Regulatory Proteins
Authors: Cheema Javairia Y. , He Jiajia , Wei Wenfan , Fu Chuanhai
Published: December 2021

In fungi, the endoplasmic reticulum-mitochondria encounter structure (ERMES) is present between the endoplasmic reticulon (ER) and mitochondria to promote the formation of the ER-mitochondria contact sites. Four constitutive components (Mmm1, Mdm12, Mdm34, and Mdm10) assemble to form the ERMES complex while regulator proteins are required for regulating the organization and function of the ERMES complex. Multiple regulator proteins, including Gem1, Lam6, Tom7, and Emr1, of the ERMES complex, have been identified recently. In this review, we discuss the organization of the ERMES complex and the roles of the regulator proteins of the ERMES complex.
The role of inflammation and neurodegeneration in diabetic macular edema
Authors: Starace Vincenzo , Battista Marco , Brambati Maria , Cavalleri Michele , Bertuzzi Federico , Amato Alessia , Lattanzio Rosangela , Bandello Francesco , Cicinelli Maria Vittoria
Published: December 2021

The pathogenesis of diabetic macular edema (DME) is complex. Persistently high blood glucose activates multiple cellular pathways and induces inflammation, oxidation stress, and vascular dysfunction. Retinal ganglion cells, macroglial and microglial cells, endothelial cells, pericytes, and retinal pigment epithelium cells are involved. Neurodegeneration, characterized by dysfunction or apoptotic loss of retinal neurons, occurs early and independently from the vascular alterations. Despite the increasing knowledge on the pathways involved in DME, only limited therapeutic strategies are available. Besides antiangiogenic drugs and intravitreal corticosteroids, alternative therapeutic options tackling inflammation, oxidative stress, and neurodegeneration have been considered, but none of them has been currently approved.
Floppy eyelid, an under-diagnosed syndrome: a review of demographics, pathogenesis, and treatment
Authors: De Gregorio Alessandra , Cerini Alberto , Scala Andrea , Lambiase Alessandro , Pedrotti Emilio , Morselli Simonetta
Published: December 2021

Floppy eyelid syndrome (FES) is a frequent eyelid disorder characterized by eyelid laxity that determines a spontaneous eyelid eversion during sleep associated with chronic papillary conjunctivitis and systemic diseases. FES is an under-diagnosed syndrome for the inaccuracy of definition and the lack of diagnostic criteria. Eyelid laxity can result from a number of involutional, local, and systemic diseases. Thus, it is pivotal to use the right terminology. When the increased distractibility of the upper or lower eyelid is an isolated condition, it is defined as ‘lax eyelid condition’ (LAC). When laxity is associated with ocular surface disorder such as papillary conjunctivitis and dry eyes, it can be referred to as ‘lax eyelid syndrome’ (LES). However, FES is characterized by the finding of a very loose upper eyelid which everts very easily and papillary tarsal conjunctivitis affecting a specific population of patients, typically male, of middle age and overweight. Obesity in middle-aged male is also recognized as the strongest risk factor in obstructive sleep apnea-hypopnea syndrome, (OSAHS). FES has been reported as the most frequent ocular disorder associated with OSAHS. Patients with FES often complain of non-pathognomonic ocular signs and symptoms such as pain, foreign body sensation, redness, photophobia, and lacrimation. Due to these clinical features, FES is often misdiagnosed while an early recognition might be important to avoid its chronic, distressing course and the associated morbidities. This review provides an updated overview on FES by describing the epidemiology, proposed pathogenesis, clinical manifestations, related ocular, and systemic diseases, and treatment options.
Genome-wide expression of the residual lung reacting to experimental Pneumonectomy
Authors: Napolioni Valerio , Bianconi Fortunato , Potenza Rossella , Carpi Francesco M. , Ludovini Vienna , Picciolini Matteo , Tofanetti Francesca R. , Bufalari Antonello , Pallotti Stefano , Poggi Camilla , Anile Marco , Daddi Niccolò , Venuta Federico , Puma Francesco , Vannucci Jacopo
Published: December 2021

Background

Acute or chronic irreversible respiratory failure may occur in patients undergoing pneumonectomy. Aim of this study was to determine transcriptome expression changes after experimental pneumonectomy in swine model. Experimental left pneumonectomy was performed in five pigs under general anaesthesia. Both the resected and the remaining lung, after 60 post-operative completely uneventful days, underwent genome-wide bulk RNA-Sequencing (RNA-Seq).

Results

Histological analysis showed dilation of air spaces and rupture of interalveolar septa. In addition, mild inflammation, no fibrosis, radial stretch of the bronchus, strong enlargement of airspaces and thinning of the blood supply were observed. Bioinformatic analyses of bulk RNA-Seq data identified 553 Differentially Expressed Genes (DEGs) at adjustedP-value below 0.001, between pre- and post-pneumonectomy. The top 10 up-regulated DEGs wereEdn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; the top 10 down-regulated DEGs wereObscn, Cdkn2b,ENSSSCG00000015738,Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365.Leveraging digital cytometry tools, no difference in cellular abundance was found between the two experimental groups, while the analysis of cell type-specific gene expression patterns highlighted a striking predominance of macrophage-specific genes among the DEGs. DAVID-based gene ontology analysis showed a significant enrichment of “Extrinsic apoptotic signaling pathway” (FDR q = 7.60 × 10− 3) and “Response to insulin” (FDR q = 7.60 × 10− 3) genes, along with an enrichment of genes involved as “Negative regulators of DDX58/IFIH1 signaling” (FDR q = 7.50 × 10− 4) found by querying the REACTOME pathway database. Gene network analyses indicated a general dysregulation of gene inter-connections.

Conclusion

This translational genomics study highlighted the existence both of individual genes, mostly dysregulated in certain cellular populations (e.g., macrophages), and gene-networks involved in pulmonary reaction after left pneumonectomy. Their involvement in lung homeostasis is largely supported by previous studies, carried out both in humans and in other animal models (under homeostatic or disease-related conditions), that adopted candidate-gene approaches. Overall, the present findings represent a preliminary assessment for future, more focused, studies on compensatory lung adaptation, pulmonary regeneration and functional reload.
Clinical characteristics of patients with bronchiectasis with nontuberculous mycobacterial disease in Mainland China: a single center cross-sectional study
Authors: Yin Hongjun , Gu Xiaoying , Wang Yimin , Fan Guohui , Lu Binghuai , Liu Min , Wang Chunlei , Cao Bin , Wang Chen
Published: December 2021

Background

The diagnosis and treatment of patients with bronchiectasis and nontuberculous mycobacterium (NTM) pulmonary disease are challenging issues and the treatment is also prolonged and depends on the species. There is limited information on patients with bronchiectasis and NTM pulmonary disease in Mainland China.

Methods

This cross-sectional study was conducted at the China–Japan Friendship Hospital, Beijing, China. Those adult patients who met the diagnostic criteria for bronchiectasis and obtained a culture result of mycobacteria from lower respiratory tract specimens or lung tissue were included in this study. A logistic regression model was used to identify the related factors in patients with NTM pulmonary disease.

Results

A total of 202 patients with bronchiectasis from 19 cities, 155 without and 47 (23.3%) with NTM pulmonary disease, were included. In all the 47 patients with NTM pulmonary disease, Mycobacterium avium complex was the most common species (66.0%), and 72.3% of them were initiated on standard anti-NTM treatment within 3 months after the diagnosis of NTM pulmonary disease. A larger proportion of patients with NTM pulmonary disease had acute exacerbations of ≥ 3 times within 1 year and were diagnosed bronchiectasis ≥ 50 years among patients with NTM pulmonary disease. The HRCT chest images revealed higher proportions of nodular shadow (100% vs. 35.3%), tree-in-bud sign (97.9% vs. 29.0%), cavities (29.8% vs. 5.8%), and airway dilation of the right middle lobe or the left lingular lobe (63.8% vs. 23.9%) in patients with NTM pulmonary disease than in those without NTM pulmonary disease (all P values = 0.001). The multivariable logistic regression model indicated that three and more abnormal features (OR 33.8; 95% CI 11.1–102.8) and main lesions of bronchial expansion in the middle or lingual lobe (OR 6.4; 95% CI 2.4–16.6) in HRCT chest images were independently associated with NTM pulmonary disease (P values = 0.001).

Conclusion

In a single center of Mainland China, > 23% of patients with bronchiectasis had NTM pulmonary disease, and most patients were started on standard treatment within 3 months after the diagnosis of NTM pulmonary disease. These findings suggest that patients with bronchiectasis should be thoroughly examined for the presence of NTM pulmonary disease.

Trial registration

NCT03594032.
Correction to: COVID-19-related acute kidney injury; incidence, risk factors and outcomes in a large UK cohort
Authors: Jewell Paul D. , Bramham Kate , Galloway James , Post Frank , Norton Sam , Teo James , Fisher Richard , Saha Rohit , Hutchings Sam , Hopkins Phil , Smith Priscilla , Joslin Jennifer , Jayawardene Satish , Mackie Sarah , Mudhaffer Ali , Holloway Amelia , Kibble Henry , Akter Mosammat , Zuckerman Benjamin , Palmer Kieran , Murphy Ciara , Iatropoulou Domniki , Sharpe Claire C. , Lioudaki Eirini
Published: December 2021

An amendment to this paper has been published and can be accessed via the original article.
Influence of contextual socioeconomic position on hypertension risk in low- and middle-income countries: disentangling context from composition
Authors: Abba Mustapha S. , Nduka Chidozie U. , Anjorin Seun , Mohamed Shukri F. , Agogo Emmanuel , Uthman Olalekan A.
Published: December 2021

Background

Hypertension has emerged as the single most significant modifiable risk factor for cardiovascular disease and death worldwide. Resource-limited settings are currently experiencing the epidemiological transition from infectious diseases to chronic non-communicable diseases, primarily due to modifications in diet and lifestyle behaviour. The objective of this study was to examine the influence of individual-, community- and country-level factors associated with hypertension in low- and middle-income countries (LMICs).

Methods

Multivariable multi-level logistic regression analysis was applied using 12 Demographic and Health Survey (DHS) datasets collected between 2011 and 2018 in LMICs. We included 888,925 respondents (Level 1) nested within 33,883 neighbourhoods (Level 2) from 12 LMICs (Level 3).

Results

The prevalence of hypertension ranged from 10.3% in the Kyrgyz Republic to 52.2% in Haiti. After adjusting for the individual-, neighbourhood- and country-level factors, we found respondents living in the least deprived areas were 14% more likely to have hypertension than those from the most deprived areas (OR = 1.14, 95% CI 1.10 to 1.17). We observed a significant variation in the odds of hypertension across the countries and the neighbourhoods. Approximately 26.3 and 47.6% of the variance in the odds of hypertension could be attributed to country- and neighbourhood-level factors, respectively. We also observed that respondents moving to a different neighbourhood or country with a higher risk of hypertension had an increased chance of developing hypertension, the median increase in their odds of hypertension was 2.83-fold (95% CI 2.62 to 3.07) and 4.04- fold (95% CI 3.98 to 4.08), respectively.

Conclusions

This study revealed that individual compositional and contextual measures of socioeconomic status were independently associated with the risk of developing hypertension. Therefore, prevention strategies should be implemented at the individual level and the socioeconomic and contextual levels to reduce the burden of hypertension.
Incidence, aetiology and clinical features of eosinophilic pleural effusion: a retrospective study
Authors: Li Minfang , Zeng Yunxiang , Li Yaqing , Jia Dan , Chen Sheng , Wang Jinlin
Published: December 2021

Background

Eosinophilic pleural effusion (EPE) is a distinct entity among pleural effusions, but its diagnostic and prognostic significance is still controversial. This study aimed to evaluate the incidence and aetiological distribution of EPE in our institution and to assess the relationship between EPE and malignancy and other underlying diseases and the relevance of the percentage of eosinophils and other laboratory parameters.

Methods

A retrospective study was conducted by reviewing the medical records of 252 patients with PE from September 2017 to January 2021.

Results

EPE was found in 34 (13.49%) out of 252 patients. There were 20 (58.82%) males and 14 (41.18%) females in the EPE group. The mean percentage of eosinophils in EPE (21.7%, range (10.0–67.5%)) was significantly higher than the percentage of eosinophils in peripheral blood (5.65%, range (0–34.60%); p < 0.05). The most common cause of EPE was malignant disease (52.94%), followed by idiopathy (14.71%), parasites (8.82%), pneumonia (8.82%) and others (14.71%). Comparative analysis of patients with malignant versus nonmalignant EPE showed that patients with malignant EPE were significantly older, and had a lower white blood cell (WBC) count in the pleural fluid (1.8 vs 4.7 cells × 109/L, p < 0.05). However, the percentage of eosinophils in PE was not significantly different between malignant EPE and nonmalignant EPE (p = 0.66). There was no correlation between the percentage of eosinophils in PE and peripheral blood (r = 0.29; p = 0.09).

Conclusions

Malignant disease ranks as the leading cause of EPE. The presence of EPE should not be considered as a predictive factor of benign conditions. Pleural parasitic infestation (PPI) should be emphasized in areas with a high incidence of parasitic disease.
Impact of COVID-19 on patient and healthcare professional attitudes, beliefs, and behaviors toward the healthcare system and on the dynamics of the healthcare pathway
Authors: Bernacki Katarzyna , Keister Angie , Sapiro Nadia , Joo Jin Su , Mattle Lisa
Published: December 2021

Background

COVID-19 has dramatically changed how healthcare is delivered and experienced.

Methods

One-on-one interviews and a virtual ethnographic roundtable were conducted among 45 patients, caregivers, and healthcare professionals (HCPs) in 4 therapeutic areas from the United States and Japan: overactive bladder, vasomotor symptoms, prostate cancer, and metastatic urothelial carcinoma. The goal was to identify the impact of COVID-19 on patient/caregiver and HCP attitudes, interactions, beliefs, and behaviors toward the healthcare system and care pathway.

Results

Four foundational themes were identified: 1) COVID-19 risk is relative; 2) isolation is collateral damage; 3) telehealth is a parallel universe; and 4) COVID-19 is destabilizing the foundations of healthcare. Numerous insights, influenced by diverse cultural, social, and psychological factors, were identified within each theme.

Conclusions

The impacts of COVID-19 were noticeable at multiple points of care during the “universal” care pathway, including at initial screening, referral to specialists, diagnosis, treatment initiation/surgery, and during ongoing care. Greater appreciation of the short- and long-term impacts of COVID-19 and resulting gaps in care may act as a catalyst for positive change in future patient care.
Modular signature of long non-coding RNA association networks as a prognostic biomarker in lung cancer
Authors: Li Albert , Yu Wen-Hsuan , Hsu Chia-Lang , Huang Hsuan-Cheng , Juan Hsueh-Fen
Published: December 2021

Background

Increasing amount of long non-coding RNAs (lncRNAs) have been found involving in many biological processes and played salient roles in cancers. However, up until recently, functions of most lncRNAs in lung cancer have not been fully discovered, particularly in the co-regulated lncRNAs. Thus, this study aims to investigate roles of lncRNA modules and uncover a module-based biomarker in lung adenocarcinoma (LUAD).

Results

We used gene expression profiles from The Cancer Genome Atlas (TCGA) to construct the lncRNA association networks, from which the highly-associated lncRNAs are connected as modules. It was found that the expression of some modules is significantly associated with patient’s survival, including module N1 (HR = 0.62, 95% CI = 0.46–0.84, p = 0.00189); N2 (HR = 0.68, CI = 0.50–0.93, p = 0.00159); N4 (HR = 0.70, CI = 0.52–0.95, p = 0.0205) and P3 (HR = 0.68, CI = 0.50–0.92, p = 0.0123). The lncRNA signature consisting of these four prognosis-related modules, a 4-modular lncRNA signature, is associated with favourable prognosis in TCGA-LUAD (HR = 0.51, CI = 0.37–0.69, p value = 2.00e−05). Afterwards, to assess the performance of the generic modular signature as a prognostic biomarker, we computed the time-dependent area under the receiver operating characteristics (AUC) of this 4-modular lncRNA signature, which showed AUC equals 68.44% on 336th day. In terms of biological functions, these modules are correlated with several cancer hallmarks and pathways, including Myc targets, E2F targets, cell cycle, inflammation/immunity-related pathways, androgen/oestrogen response, KRAS signalling, DNA repair and epithelial-mesenchymal transition (EMT).

Conclusion

Taken together, we identified four novel LUAD prognosis-related lncRNA modules, and assessed the performance of the 4-modular lncRNA signature being a prognostic biomarker. Functionally speaking, these modules involve in oncogenic hallmarks as well as pathways. The results unveiled the co-regulated lncRNAs in LUAD and may provide a framework for further lncRNA studies in lung cancer.
Impact of perioperative use of GnRH agonist or dienogest on ovarian reserve after cystectomy for endometriomas: a randomized controlled trial
Authors: Muraoka Ayako , Osuka Satoko , Yabuki Atsushi , Bayasula  , Yoshihara Masato , Tanaka Hideaki , Sonehara Reina , Miyake Natsuki , Murakami Mayuko , Yoshita Sayako , Nakanishi Natsuki , Nakamura Tomoko , Goto Maki , Iwase Akira , Kajiyama Hiroaki
Published: December 2021

Background

Ovarian endometrioma is a common gynecological disease that is often treated with surgery or hormonal treatment. Ovarian cystectomy, a surgical procedure for ovarian endometrioma, can result in impaired ovarian reserve.

Methods

We conducted a randomized controlled trial to evaluate the efficacy of hormonal treatment [gonadotropin-releasing hormone agonist (GnRHa) or dienogest (DNG)] for preserving ovarian reserve after cystectomy for ovarian endometrioma. The primary endpoint was the level of serum Anti-Müllerian hormone (AMH) as a marker of ovarian reserve.

Results

Before and after laparoscopic surgery, 22 patients in the GnRHa group and 27 patients in the DNG group were administered hormonal treatment for a total of 4 months. After 1-year follow-up, >60% of the patients in the DNG group retained over 70% of their pretreatment AMH levels, whereas no patient in the GnRHa group retained their AMH levels after cystectomy (P < 0.01). Interleukin-6 (IL-6) is a key cytokine involved in inflammation. Compared with the GnRHa group, patients in the DNG group had lower IL-6 levels at the end of treatment.

Conclusions

Our data revealed that DNG is more effective than GnRHa in preserving ovarian reserve after cystectomy of ovarian endometrioma. This is achieved through the reduction of the inflammatory response during the perioperative period and other endometriosis-related inflammatory reactions.

Trial registration

The registration number of this trial is UMIN-CTR, UMIN000018569, registered 6 August 2015, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021492, and Japan Registry of Clinical Trials, jRCTs041180140, registered 29 March 2019, https://jrct.niph.go.jp/en-latest-detail/jRCTs041180140. This randomized controlled trial was conducted in accordance with the CONSORT guidelines.
Digging deeper: exploring chiropractors online claims about non-musculoskeletal disorders
Authors: O’Neill Søren , Wahlqvist Anneline Bugge , Simonsen Natasja Kragh , Myburgh Cornelius , Jensen Rikke Krüger
Published: December 2021

Background

Some chiropractors suggest that chiropractic treatment is appropriate for health issues other than musculoskeletal problems. The prevalence of such claims on individual clinic websites has previously been reported as approximately one-in-four in Denmark. The underlying rationales for such claims may reflect convictions about traditional chiropractic subluxations paradigms, but are not self-evident and has not previously been studied.

Methods

An exploratory qualitative case interview study of Danish chiropractors with websites which contain claims about chiropractic efficacy in the treatment of non-musculoskeletal disorders. Websites were identified from a nation wide random sample (57%) of all chiropractic clinic websites.

Results

Of the original 139 websites, 36 were identified as mentioning non-MSK conditions. When revisited, 19 of those clinic websites still mentioned non-MSK disorders and were contacted. Eleven (11) declined our invitation to participate. Interviews were conducted with the responsible chiropractor from each of the remaining 8 clinics.

Five distinct themes were identified in the rationales for treating non-musculoskeletal disorders: ‘Positive side-effects,’ ‘Experience,’ ‘Web page,’ ‘Communication’ and ‘Conviction.’

Conclusions

A minority of Danish chiropractic websites suggest that non-musculoskeletal disorders are within the chiropractic scope of practice. Those that do, do so for varying reasons—poor communication and website maintenance were commonly cited problems. An explicitly stated adherence to traditional chiropractic subluxations concepts was uncommon. By contrast, a more tempered rationale that suggested a potential beneficial side-effect of chiropractic on non-musculoskeletal health issues were more common and was typically presented in softer-language and/or with some reservations.
Comparative analysis of long-term oncologic outcomes for minimally invasive and open Ivor Lewis esophagectomy after neoadjuvant chemoradiation: a propensity score matched observational study
Authors: Merritt Robert E. , Kneuertz Peter J. , Abdel-Rasoul Mahmoud , D’Souza Desmond M. , Perry Kyle A.
Published: December 2021

Background

Locally advanced esophageal carcinoma is typically treated with neoadjuvant chemoradiation and esophagectomy (trimodality therapy). We compared the long-term oncologic outcomes of minimally invasive Ivor Lewis esophagectomy (M-ILE) cohort with a propensity score weighted cohort of open Ivor Lewis esophagectomy (O-ILE) cases after trimodality therapy.

Methods

This is a retrospective review of 223 patients diagnosed with esophageal carcinoma who underwent neoadjuvant chemoradiation followed by M-ILE or O-ILE from April 2009 to February 2019. Inverse probability of treatment weighting (IPTW) adjustment was used to balance the baseline characteristics between study groups. Kaplan–Meier survival curves were calculated for overall survival and recurrence-free survival comparing the two groups. Multivariate Cox proportional hazards regression models were used to determine predictive variables for overall and recurrence-free survival.

Results

The IPTW cohort included patients with esophageal carcinoma who underwent M-ILE (n = 142) or O-ILE (n = 68). The overall rate of postoperative adverse events was not significantly different after IPTW adjustment between the O-ILE and M-ILE trimodality groups (53.4% vs. 39.2%, p = 0.089). The 3-year overall survival (OS) for the M-ILE group was 59.4% (95% CI: 49.8–67.8) compared to 55.7% (95% CI: 39.2–69.4) for the O-ILE group (p = 0.670). The 3-year recurrence-free survival for the M-ILE group was 59.9% (95% CI: 50.2–68.2) compared to 61.6% (95% CI: 41.9–76.3) for the O-ILE group (p = 0.357). A complete response to neoadjuvant chemoradiation was significantly predictive of improved OS and RFS.

Conclusion

The overall and recurrence-free survival rates for M-ILE were not significantly different from O-ILE for esophageal carcinoma after trimodality therapy. Complete response to neoadjuvant chemoradiation was predictive of improved overall and recurrence- free survival.
HSV-1 reactivation is associated with an increased risk of mortality and pneumonia in critically ill COVID-19 patients
Authors: Meyer Antoine , Buetti Niccolò , Houhou-Fidouh Nadhira , Patrier Juliette , Abdel-Nabey Moustafa , Jaquet Pierre , Presente Simona , Girard Tiphaine , Sayagh Faiza , Ruckly Stephane , Wicky Paul-Henri , de Montmollin Etienne , Bouadma Lila , Sonneville Romain , Descamps Diane , Timsit Jean-Francois
Published: December 2021

Background

Data in the literature about HSV reactivation in COVID-19 patients are scarce, and the association between HSV-1 reactivation and mortality remains to be determined. Our objectives were to evaluate the impact of Herpes simplex virus (HSV) reactivation in patients with severe SARS-CoV-2 infections primarily on mortality, and secondarily on hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) and intensive care unit-bloodstream infection (ICU-BSI).

Methods

We conducted an observational study using prospectively collected data and HSV-1 blood and respiratory samples from all critically ill COVID-19 patients in a large reference center who underwent HSV tests. Using multivariable Cox and cause-specific (cs) models, we investigated the association between HSV reactivation and mortality or healthcare-associated infections.

Results

Of the 153 COVID-19 patients admitted for ≥ 48 h from Feb-2020 to Feb-2021, 40/153 (26.1%) patients had confirmed HSV-1 reactivation (19/61 (31.1%) with HSV-positive respiratory samples, and 36/146 (24.7%) with HSV-positive blood samples. Day-60 mortality was higher in patients with HSV-1 reactivation (57.5%) versus without (33.6%, p = 0.001). After adjustment for mortality risk factors, HSV-1 reactivation was associated with an increased mortality risk (hazard risk [HR] 2.05; 95% CI 1.16–3.62; p = 0.01). HAP/VAP occurred in 67/153 (43.8%) and ICU-BSI in 42/153 (27.5%) patients. In patients with HSV-1 reactivation, multivariable cause-specific models showed an increased risk of HAP/VAP (csHR 2.38, 95% CI 1.06–5.39, p = 0.037), but not of ICU-BSI.

Conclusions

HSV-1 reactivation in critically ill COVID-19 patients was associated with an increased risk of day-60 mortality and HAP/VAP.
The SEQC2 epigenomics quality control (EpiQC) study
Authors: Foox Jonathan , Nordlund Jessica , Lalancette Claudia , Gong Ting , Lacey Michelle , Lent Samantha , Langhorst Bradley W. , Ponnaluri V. K. Chaithanya , Williams Louise , Padmanabhan Karthik Ramaswamy , Cavalcante Raymond , Lundmark Anders , Butler Daniel , Mozsary Christopher , Gurvitch Justin , Greally John M. , Suzuki Masako , Menor Mark , Nasu Masaki , Alonso Alicia , Sheridan Caroline , Scherer Andreas , Bruinsma Stephen , Golda Gosia , Muszynska Agata , Łabaj Paweł P. , Campbell Matthew A. , Wos Frank , Raine Amanda , Liljedahl Ulrika , Axelsson Tomas , Wang Charles , Chen Zhong , Yang Zhaowei , Li Jing , Yang Xiaopeng , Wang Hongwei , Melnick Ari , Guo Shang , Blume Alexander , Franke Vedran , Ibanez de Caceres Inmaculada , Rodriguez-Antolin Carlos , Rosas Rocio , Davis Justin Wade , Ishii Jennifer , Megherbi Dalila B. , Xiao Wenming , Liao Will , Xu Joshua , Hong Huixiao , Ning Baitang , Tong Weida , Akalin Altuna , Wang Yunliang , Deng Youping , Mason Christopher E.
Published: December 2021

Background

Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify types of cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and cross-validated resource for epigenetics research from the FDA’s Epigenomics Quality Control Group.

Results

Each sample is processed in multiple replicates by three whole-genome bisulfite sequencing (WGBS) protocols (TruSeq DNA methylation, Accel-NGS MethylSeq, and SPLAT), oxidative bisulfite sequencing (TrueMethyl), enzymatic deamination method (EMSeq), targeted methylation sequencing (Illumina Methyl Capture EPIC), single-molecule long-read nanopore sequencing from Oxford Nanopore Technologies, and 850k Illumina methylation arrays. After rigorous quality assessment and comparison to Illumina EPIC methylation microarrays and testing on a range of algorithms (Bismark, BitmapperBS, bwa-meth, and BitMapperBS), we find overall high concordance between assays, but also differences in efficiency of read mapping, CpG capture, coverage, and platform performance, and variable performance across 26 microarray normalization algorithms.

Conclusions

The data provided herein can guide the use of these DNA reference materials in epigenomics research, as well as provide best practices for experimental design in future studies. By leveraging seven human cell lines that are designated as publicly available reference materials, these data can be used as a baseline to advance epigenomics research.
geneBasis: an iterative approach for unsupervised selection of targeted gene panels from scRNA-seq
Authors: Missarova Alsu , Jain Jaison , Butler Andrew , Ghazanfar Shila , Stuart Tim , Brusko Maigan , Wasserfall Clive , Nick Harry , Brusko Todd , Atkinson Mark , Satija Rahul , Marioni John C.
Published: December 2021

scRNA-seq datasets are increasingly used to identify gene panels that can be probed using alternative technologies, such as spatial transcriptomics, where choosing the best subset of genes is vital. Existing methods are limited by a reliance on pre-existing cell type labels or by difficulties in identifying markers of rare cells. We introduce an iterative approach, geneBasis, for selecting an optimal gene panel, where each newly added gene captures the maximum distance between the true manifold and the manifold constructed using the currently selected gene panel. Our approach outperforms existing strategies and can resolve cell types and subtle cell state differences.
Evaluating the efficacy, impact, and feasibility of community-based house screening as a complementary malaria control intervention in southern Africa: a study protocol for a household randomized trial
Authors: Sangoro Onyango P. , Fillinger Ulrike , Saili Kochelani , Nkya Theresia Estomih , Marubu Rose , Masaninga Freddie , Trigo Sonia Casimiro , Tarumbwa Casper , Hamainza Busiku , Baltazar Candrinho , Mberikunashe Joseph , Chisanga Brian , Menale Kassie , Chanda Emmanuel , Mutero Clifford Maina
Published: December 2021

Background

Concerted effort to control malaria has had a substantial impact on the transmission of the disease in the past two decades. In areas where reduced malaria transmission is being sustained through insecticide-based vector control interventions, primarily long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), non-insecticidal complementary tools will likely be needed to push towards malaria elimination. Once interruption in local disease transmission is achieved, insecticide-based measures can be scaled down gradually and eventually phased out, saving on costs of sustaining control programs and mitigating any unintended negative health and environmental impacts posed by insecticides. These non-insecticidal methods could eventually replace insecticidal methods of vector control.

House screening, a non-insecticidal method, has a long history in malaria control, but is still not widely adopted in sub-Saharan Africa. This study aims to add to the evidence base for this intervention in low transmission settings by assessing the efficacy, impact, and feasibility of house screening in areas where LLINs are conventionally used for malaria control.

Methods

A two-armed, household randomized clinical trial will be conducted in Mozambique, Zambia, and Zimbabwe to evaluate whether combined the use of house screens and LLINs affords better protection against clinical malaria in children between 6 months and 13 years compared to the sole use of LLINs. Eight hundred households will be enrolled in each study area, where 400 households will be randomly assigned the intervention, house screening, and LLINs while the control households will be provided with LLINs only. Clinical malaria incidence will be estimated by actively following up one child from each household for 6 months over the malaria transmission season. Cross-sectional parasite prevalence will be estimated by testing all participating children for malaria parasites at the beginning and end of each transmission season using rapid diagnostic tests.

CDC light traps and pyrethrum spray catches (PSC) will be used to sample adult mosquitoes and evaluate the impact of house screening on indoor mosquito density, species distribution, and sporozoite rates.

Discussion

This study will contribute epidemiological data on the impact of house screening on malaria transmission and assess the feasibility of its implementation on a programmatic scale.

Trial registration

ClinicalTrials.gov PACTR202008524310568. Registered on August 11, 2020.
The COPE-Trial—Communicating prognosis to parents in the neonatal ICU: Optimistic vs. PEssimistic: study protocol for a randomized controlled crossover trial using two different scripted video vignettes to explore communication preferences of parents of preterm infants
Authors: Forth Fiona A. , Hammerle Florian , König Jochem , Urschitz Michael S. , Neuweiler Philipp , Mildenberger Eva , Kidszun André
Published: December 2021

Background

One of the numerous challenges preterm birth poses for parents and physicians is prognostic disclosure. Prognoses are based on scientific evidence and medical experience. They are subject to individual assessment and will generally remain uncertain with regard to the individual. This can result in differences in prognostic framing and thus affect the recipients’ perception. In neonatology, data on the effects of prognostic framing are scarce. In particular, it is unclear whether parents prefer a more optimistic or a more pessimistic prognostic framing.

Objective

To explore parents’ preferences concerning prognostic framing and its effects on parent-reported outcomes and experiences. To identify predictors (demographic, psychological) of parents’ communication preferences.

Design, setting, participants

Unblinded, randomized controlled crossover trial (RCT) at the Division of Neonatology of the University Medical Center Mainz, Germany, including German-speaking parents or guardians of infants born preterm between 2010 and 2019 with a birth weight < 1500 g. Inclusion of up to 204 families is planned, with possible revision according to a blinded sample size reassessment.

Intervention

Embedded in an online survey and in pre-specified order, participants will watch two video vignettes depicting a more optimistic vs. a more pessimistic framing in prognostic disclosure to parents of a preterm infant. Apart from prognostic framing, all other aspects of physician-parent communication are standardized in both videos.

Main outcomes and measures

At baseline and after each video, participants complete a two-part online questionnaire (baseline and post-intervention). Primary outcome is the preference for either a more optimistic or a more pessimistic prognostic framing. Secondary outcomes include changes in state-anxiety (STAI-SKD), satisfaction with prognostic framing, evaluation of prognosis, future optimism and hope, preparedness for shared decision-making (each assessed using customized questions), and general impression (customized question), professionalism (adapted from GMC Patient Questionnaire) and compassion (Physician Compassion Questionnaire) of the consulting physician.

Discussion

This RCT will explore parents’ preferences concerning prognostic framing and its effects on physician-parent communication. Results may contribute to a better understanding of parental needs in prognostic disclosure and will be instrumental for a broad audience of clinicians, scientists, and ethicists.

Trial registration

German Clinical Trials Register DRKS00024466. Registered on April 16, 2021.