bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excess mortality during the COVID-19 pandemic in low-and lower-middle-income countries: a systematic review and meta-analysis
Authors: Gmanyami Jonathan Mawutor , Quentin Wilm , Lambert Oscar , Jarynowski Andrzej , Belik Vitaly , Amuasi John Humphrey 
Published: June 2024

Abstract
Background
Although the COVID-19 pandemic claimed a great deal of lives, it is still unclear how it affected mortality in low- and lower-middle-income countries (LLMICs). This review summarized the available literature on excess mortality during the COVID-19 pandemic in LLMICs, including methods, sources of data, and potential contributing factors that might have influenced excess mortality.

Methods
We conducted a systematic review and meta-analysis on excess mortality during the COVID-19 pandemic in LLMICs in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines We searched PubMed, Embase, Web of Science, Cochrane Library, Google Scholar, and Scopus. We included studies published from 2019 onwards with a non-COVID-19 period of at least one year as a comparator. The meta-analysis included studies reporting data on population size, as well as observed and expected deaths. We used the Mantel–Haenszel method to estimate the pooled risk ratio with 95% confidence intervals. The protocol was registered in PROSPERO (ID: CRD42022378267).

Results
The review covered 29 countries, with 10 countries included in the meta-analysis. The pooled meta-analysis included 1,405,128,717 individuals, for which 2,152,474 deaths were expected, and 3,555,880 deaths were reported. Calculated excess mortality was 100.3 deaths per 100,000 population per year, with an excess risk of death of 1.65 (95% CI: 1.649, 1.655, p < 0.001). The data sources used in the studies included civil registration systems, surveys, public cemeteries, funeral counts, obituary notifications, burial site imaging, and demographic surveillance systems. The primary techniques used to estimate excess mortality were statistical forecast modelling and geospatial analysis. One out of the 24 studies found higher excess mortality in urban settings.

Conclusion
Our findings demonstrate that excess mortality in LLMICs during the pandemic was substantial. However, estimates of excess mortality are uncertain due to relatively poor data. Understanding the drivers of excess mortality, will require more research using various techniques and data sources.
Current trends in the medical treatment of neuropathic low back pain: a Swedish registry-based study of 1.7 million people
Authors: Nyqvist Linus , Åkerstedt Josefin , Thoreson Olof 
Published: June 2024

Abstract
Background
Low back pain, a common problem worldwide, causes more global disability than any other condition and is associated with high costs to society. This observational registry-based study describes the current trends in the medical treatment of neuropathic low back pain in the Swedish region of Västra Götaland, which has a population of 1.7 million. The study aims to; (1) identify the prevalence of neuropathic low back pain within the study population; (2) to explore the patterns of medical treatment utilization, including the prevalence and distribution of opioids (OG) and analgesics specified for neuropathic low back pain (NG) and (3) to evaluate the long-term trends and changes in medical treatment practice for neuropathic low back pain over the study period.

Methods
This study includes a descriptive analysis of aggregated data extracted from the Swedish primary care registry VEGA and the pharmaceutical prescription registry Digitalis between the years 2017 and 2021. The data were stratified by year, age, gender, pharmaceutical code (ATC), and sub-diagnoses and presented as the prevalence of unique patients retrieving prescribed medication within six months before or after a registered diagnosis of neuropathic low back pain. The pharmaceutical codes were furthermore grouped into two groups depending on their mechanism of action; opioid group (OG) and neuropathic group (NG).

Results
In all four diagnosis groups, more patients used opioid analgesics than neuropathic analgesics. The greatest difference between the opioid group and neuropathic group was in the lumbar spinal stenosis diagnosis group (67.1% vs. 40.6%), followed by the lumbar root canal stenosis diagnosis (65.9% vs. 44.2%), the nerve root and plexus compressions in intervertebral disc disorders diagnosis (57.5% vs. 40.8%), and lumbago with sciatica diagnosis (38.4% vs. 22.7%).

Conclusions
The trends suggest a general increase in the prescription rate and therefore patients’ use of neuropathic analgesics for neuropathic pain associated with the studied diagnoses. However, opioid treatment remains the most common. The results indicate that the treatment for neuropathic low back pain needs to be improved.
Paradoxical effect of dopamine-agonists on IGF-1 in patients with prolactinoma: the role of weight
Authors: Caprio S. , Pilli T. , Cantara S. , Sestini F. , Fioravanti C. , Ciuoli C. , Dalmiglio C. , Corbo A. , Castagna M. G. 
Published: June 2024

Abstract
Purpose
An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index.

Methods
We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55).

Results
IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04).

Conclusions
Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.
Mixed-methods study of medical students’ attitudes toward peer physical examinations in Japan
Authors: Suzuki Emily , Nawa Nobutoshi , Okada Eriko , Akaishi Yu , Kashimada Ayako , Numasawa Mitsuyuki , Yamaguchi Kumiko , Takada Kazuki , Yamawaki Masanaga 
Published: June 2024

Abstract
Background
Most Japanese medical schools likely continue to rely on peer physical examination (PPE) as a tool to for teaching physical examination skills to students. However, the attitudes of medical students in Japan toward PPEs have not be identified. Therefore, we evaluated students’ attitudes toward PPE in a Japanese medical school as a preparation for developing a PPE policy tailored to the context of Japanese culture.

Methods
We conducted a mixed-methods study with an explanatory sequential approach, in which qualitative data were used to interpret the quantitative findings. Surveys and interviews were conducted with medical students and junior residents at a Japanese university. A total of 63 medical students and 50 junior residents responded to the questionnaire. We interviewed 16 participants to reach theoretical saturation and investigated the attitudes of medical students toward PPE and the themes emerging from the interview data, providing detailed descriptions of the quantitative findings.

Results
Female participants were significantly more likely than male participants to report varying degrees of resistance to being a model patient during PPE (male: 59.7%, female: 87%, p < 0.001). Most of the participants who took on the role of patients that involved undressing were males. The participants expected improvements in issues related to the guarantee of freedom to refuse to be a model patient and measures to protect confidentiality. Approximately 22% of the participants reported that they witnessed incidental findings (including variations within the normal range) in front of other students during PPE.

Conclusions
The findings imply that medical students expect high levels of autonomy and confidentiality when volunteering as model patients during PPE. Thus, developing a PPE policy suitable for Japanese culture may be effective in establishing a student-centered PPE environment.
Associations of serum uric acid variability with neuroimaging metrics and cognitive decline: a population-based cohort study
Authors: Lv Han , Sun Jing , Zhang Tong , Hui Ying , Li Jing , Zhao Xinyu , Chen Shuohua , Liu Wenjuan , Li Xiaoshuai , Zhao Pengfei , Wu Shouling , Liu Yanying , Wang Zhenchang 
Published: June 2024

Abstract
Background
The relationship between variation in serum uric acid (SUA) levels and brain health is largely unknown. This study aimed to examine the associations of long-term variability in SUA levels with neuroimaging metrics and cognitive function.

Methods
This study recruited 1111 participants aged 25–83 years from a multicenter, community-based cohort study. The SUA concentrations were measured every two years from 2006 to 2018. We measured the intraindividual SUA variability, including the direction and magnitude of change by calculating the slope value. The associations of SUA variability with neuroimaging markers (brain macrostructural volume, microstructural integrity, white matter hyperintensity, and the presence of cerebral small vessel disease) and cognitive function were examined using generalized linear models. Mediation analyses were performed to assess whether neuroimaging markers mediate the relationship between SUA variation and cognitive function.

Results
Compared with the stable group, subjects with increased or decreased SUA levels were all featured by smaller brain white matter volume (beta =  − 0.25, 95% confidence interval [CI] − 0.39 to − 0.11 and beta =  − 0.15, 95% CI − 0.29 to − 0.02). Participants with progressively increased SUA exhibited widespread disrupted microstructural integrity, featured by lower global fractional anisotropy (beta =  − 0.24, 95% CI − 0.38 to − 0.10), higher mean diffusivity (beta = 0.16, 95% CI 0.04 to 0.28) and radial diffusivity (beta = 0.19, 95% CI 0.06 to 0.31). Elevated SUA was also associated with cognitive decline (beta =  − 0.18, 95% CI − 0.32 to − 0.04). White matter atrophy and impaired brain microstructural integrity mediated the impact of SUA increase on cognitive decline.

Conclusions
It is the magnitude of SUA variation rather than the direction that plays a critical negative role in brain health, especially for participants with hyperuricemia. Smaller brain white matter volume and impaired microstructural integrity mediate the relationship between increased SUA level and cognitive function decline. Long-term stability of SUA level is recommended for maintaining brain health and preventing cognitive decline.
Impact of baseline cardiovascular risk on the outcomes of intensive blood pressure intervention: a post hoc analysis of the China rural hypertension control project
Authors: Sun Guozhe , Wang Chang , Ye Ning , Shi Chuning , Ouyang Nanxiang , Qiao Lixia , Li Guangxiao , Zhang Linlin , Yu Yao , Li Zhi , Zhou Ying , Chen Zihan , Zhang Shu , Zhang Pengyu , Geng Danxi , Miao Wei , Liu Songyue , Sun Yingxian 
Published: June 2024

Abstract
Background
The 2018/2023 ESC/ESH Guidelines underlined a gap how baseline cardiovascular disease (CVD) risk predicted blood pressure (BP) lowering benefits. Further, 2017 ACC/AHA Guideline and 2021 WHO Guideline recommended implementation studies about intensive BP control. Now, to bridge these guideline gaps, we conducted a post hoc analysis to validate whether the baseline CVD risk influences the effectiveness of the intensive BP control strategy, which was designed by China Rural Hypertension Control Project (CRHCP).

Methods
This is a post hoc analysis of CRHCP, among which participants were enrolled except those having CVD history, over 80 years old, or missing data. Subjects were stratified into quartiles by baseline estimated CVD risk and then grouped into intervention and usual care group according to original assignment in CRHCP. Participants in the intervention group received an integrated, multi-faceted treatment strategy, executed by trained non-physician community health-care providers, aiming to achieve a BP target of < 130/80 mmHg. Cox proportional-hazards models were used to estimate the hazard ratios of outcomes for intervention in each quartile, while interaction effect between intervention and estimated CVD risk quartiles was additionally assessed. The primary outcome comprised myocardial infarction, stroke, hospitalization for heart failure, or CVD deaths.

Results
Significant lower rates of primary outcomes for intervention group compared with usual care for each estimated CVD risk quartile were reported. The hazard ratios (95% confidence interval) in the four quartiles (from Q1 to Q4) were 0.59 (0.40, 0.87), 0.54 (0.40, 0.72), 0.72 (0.57, 0.91) and 0.65 (0.53, 0.80), respectively (all Ps < 0.01). There’s no significant difference of hazard ratios by intervention across risk quartiles (P for interaction = 0.370). Only the relative risk of hypotension, not symptomatic hypotension, was elevated in the intervention group among upper three quartiles.

Conclusions
Intensive BP lowering strategy designed by CRHCP group was effective and safe in preventing cardiovascular events independent of baseline CVD risk.

Trial registration
The trial is registered with ClinicalTrials.gov, NCT03527719.
Expression profile of long noncoding RNAs and comprehensive analysis of lncRNA-cisTF-DGE regulation in condyloma acuminatum
Authors: Xie Bo , Wu Yinhua , Wang Su , Ruan Liming , Liu Xiaoyan 
Published: June 2024

Abstract
Objective
To identify differentially expressed long noncoding RNAs (lncRNAs) in condyloma acuminatum (CA) and to explore their probable regulatory mechanisms by establishing coexpression networks.

Methods
High-throughput RNA sequencing was performed to assess genome-wide lncRNA expression in CA and paired adjacent mucosal tissue. The expression of candidate lncRNAs and their target genes in larger CA specimens was validated using real-time quantitative reverse transcriptase polymerase chain reaction (RT‒qPCR). Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for the functional enrichment analysis of these candidate lncRNAs and differential mRNAs. The coexpressed mRNAs of the candidate lncRNAs, calculated by Pearson’s correlation coefficient, were also analysed using GO and KEGG analysis. In addition, the interactions among differentially expressed lncRNAs (DElncRNAs)-cis-regulatory transcription factors (cisTFs)-differentially expressed genes (DEGs) were analysed and their network was constructed.

Results
A total of 546 lncRNAs and 2553 mRNAs were found to be differentially expressed in CA compared to the paired control. Functional enrichment analysis revealed that the DEGs coexpressed with DElncRNAs were enriched in the terms of cell adhesion and keratinocyte differentiation, and the pathways of ECM-receptor interaction, local adhesion, PI3K/AKT and TGF-ß signaling. We further constructed the network among DElncRNAs-cisTFs-DEGs and found that these 95 DEGs were mainly enriched in GO terms of epithelial development, regulation of transcription or gene expression. Furthermore, the expression of 3 pairs of DElncRNAs and cisTFs, EVX1-AS and HOXA13, HOXA11-AS and EVX1, and DLX6-AS and DLX5, was validated with a larger number of specimens using RT‒qPCR.

Conclusion
CA has a specific lncRNA profile, and the differentially expressed lncRNAs play regulatory roles in mRNA expression through cis-acting TFs, which provides insight into their regulatory networks. It will be useful to understand the pathogenesis of CA to provide new directions for the prevention, clinical treatment and efficacy evaluation of CA.
Detection of Duffy blood group genotypes and submicroscopic Plasmodium infections using molecular diagnostic assays in febrile malaria patients
Authors: Abagero Beka R. , Rama Rei , Obeid Abdulghani , Tolosa Tirusew , Lukas Biniyam , Teka Taye , Tesfaye Daniel , Lo Eugenia , Yewhalaw Delenasaw 
Published: June 2024

Abstract
Background
Malaria remains a severe parasitic disease, posing a significant threat to public health and hindering economic development in sub-Saharan Africa. Ethiopia, a malaria endemic country, is facing a resurgence of the disease with a steadily rising incidence. Conventional diagnostic methods, such as microscopy, have become less effective due to low parasite density, particularly among Duffy-negative human populations in Africa. To develop comprehensive control strategies, it is crucial to generate data on the distribution and clinical occurrence of Plasmodium vivax and Plasmodium falciparum infections in regions where the disease is prevalent. This study assessed Plasmodium infections and Duffy antigen genotypes in febrile patients in Ethiopia.

Methods
Three hundred febrile patients visiting four health facilities in Jimma town of southwestern Ethiopia were randomly selected during the malaria transmission season (Apr–Oct). Sociodemographic information was collected, and microscopic examination was performed for all study participants. Plasmodium species and parasitaemia as well as the Duffy genotype were assessed by quantitative polymerase chain reaction (qPCR) for all samples. Data were analysed using Fisher’s exact test and kappa statistics.

Results
The Plasmodium infection rate by qPCR was 16% (48/300) among febrile patients, of which 19 (39.6%) were P. vivax, 25 (52.1%) were P. falciparum, and 4 (8.3%) were mixed (P. vivax and P. falciparum) infections. Among the 48 qPCR-positive samples, 39 (13%) were negative by microscopy. The results of bivariate logistic regression analysis showed that agriculture-related occupation, relapse and recurrence were significantly associated with Plasmodium infection (P < 0.001). Of the 300 febrile patients, 85 (28.3%) were Duffy negative, of whom two had P. vivax, six had P. falciparum, and one had mixed infections. Except for one patient with P. falciparum infection, Plasmodium infections in Duffy-negative individuals were all submicroscopic with low parasitaemia.

Conclusions
The present study revealed a high prevalence of submicroscopic malaria infections. Plasmodium vivax infections in Duffy-negative individuals were not detected due to low parasitaemia. In this study, an improved molecular diagnostic tool was used to detect and characterize Plasmodium infections, with the goal of quantifying P. vivax infection in Duffy-negative individuals. Advanced molecular diagnostic techniques, such as multiplex real-time PCR, loop-mediated isothermal amplification (LAMP), and CRISPR-based diagnostic methods. These techniques offer increased sensitivity, specificity, and the ability to detect low-parasite-density infections compared to the employed methodologies.
Does commercialization lead to more intensive management strategies? Decision-making for the utilization of non-timber forest products in a Nahua area of the Sierra Negra, Mexico
Authors: Miranda-Gamboa Myriam A. , Martínez-Ballesté Andrea , Ricker Martin , Casas Alejandro , Blancas José 
Published: June 2024

Abstract
Background
The commercialization of non-timber forest products (NTFPs) provides income for rural indigenous households. The integration of NTFPs into formal markets tends to intensify management practices to ensure production and monetary benefits. However, more research is needed to understand the motivations for managing of commercialized species. We examine the influence of social, ecological, and economic factors on traditional management and how they drive the adoption of more or less intensive practices for subsistence and commercially traded NTFPs.

Methods
The study was conducted in the Nahua community of Ixtacxochitla, in the Sierra Negra of central Mexico, where we conducted free lists and semi-structured interviews in 32% of the 88 households to assess socio-ecological variables related to management practices. In addition, we interviewed local traders to assess commercial variables used in a cost–benefit model to calculate the net annual income of commercialized species. Non-metric multidimensional scaling was used to analyze relationships between socio-ecological variables and management practices. We also explored the relationship between management and commercial factors using principal component analysis.

Results
We recorded 64 plant and mushroom species of NTFPs used for medicinal, ornamental, ceremonial, and edible purposes, 36 of which are commercialized in the municipal market of Coyomeapan. The commercialized species generated an average annual net income of MXN 67,526 (USD 3924) per family, with five species contributing the most. Species both used for both subsistence and commercialization were managed through incipient in situ gathering, tolerance in ex situ anthropogenic areas, and intensive protection and propagation efforts in ex situ environments. Even the five species with the highest commercial returns were managed across this gradient of practices. Key factors influencing the adoption of more intensive species management practices were feasibility of management, type of species use, ecological abundance, frequency of consumption, and cultural importance.

Conclusions
The intensification of NTFPs management is not solely driven by the commercial value of the products or the level of income generated. Instead, the interaction between socio-ecological and economic factors determines the extent of management practices. The main constraint to the implementation of intensive practices has been the inability to manage species outside their natural habitats, despite their cultural significance and frequent consumption. Understanding the factors involved in the harvesting of NTFPs can serve as the basis for future research aimed at analyzing the conditions for successful and sustainable NTFPs commercialization.