bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of mutations in the cysteine desulfurase IscS (Pfnfs1) gene in recurrent Plasmodium falciparum infections following artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) treatment in Matayos, Western Kenya
Authors: Gachie Beatrice , Thiong’o Kelvin , Muriithi Brenda , Chepngetich Jean , Onchieku Noah , Gathirwa Jeremiah , Mwitari Peter , Magoma Gabriel , Kiboi Daniel , Kimani Francis 
Published: May 2023

Abstract
Background
Malaria remains a public health concern globally. Resistance to anti-malarial drugs has consistently threatened the gains in controlling the malaria parasites. Currently, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the treatment regimens against Plasmodium falciparum infections in many African countries, including Kenya. Recurrent infections have been reported in patients treated with AL or DP, suggesting the possibility of reinfection or parasite recrudescence associated with the development of resistance against the two therapies. The Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) K65 selection marker has previously been associated with decreased lumefantrine susceptibility. This study evaluated the frequency of the Pfnfs1 K65 resistance marker and associated K65Q resistant allele in recurrent infections collected from P. falciparum-infected individuals living in Matayos, Busia County, in western Kenya.

Methods
Archived dried blood spots (DBS) of patients with recurrent malaria infection on clinical follow-up days after treatment with either AL or DP were used in the study. After extraction of genomic DNA, PCR amplification and sequencing analysis were employed to determine the frequencies of the Pfnfs1 K65 resistance marker and K65Q mutant allele in the recurrent infections. Plasmodium falciparum msp1 and P. falciparum msp2 genetic markers were used to distinguish recrudescent infections from new infections.

Results
The K65 wild-type allele was detected at a frequency of 41% while the K65Q mutant allele was detected at a frequency of 22% in the recurrent samples. 58% of the samples containing the K65 wild-type allele were AL treated samples and while 42% were DP treated samples. 79% of the samples with the K65Q mutation were AL treated samples and 21% were DP treated samples. The K65 wild-type allele was detected in three recrudescent infections (100%) identified from the AL treated samples. The K65 wild-type allele was detected in two recrudescent DP treated samples (67%) while the K65Q mutant allele was identified in one DP treated (33%) recrudescent sample.

Conclusions
The data demonstrate a higher frequency of the K65 resistance marker in patients with recurrent infection during the study period. The study underscores the need for consistent monitoring of molecular markers of resistance in regions of high malaria transmission.
Anti-malarial resistance in Mozambique: Absence of Plasmodium falciparum Kelch 13 (K13) propeller domain polymorphisms associated with resistance to artemisinins
Authors: da Silva Clemente , Matias Daniela , Dias Brigite , Cancio Beatriz , Silva Miguel , Viegas Ruben , Chivale Nordino , Luis Sonia , Salvador Crizolgo , Duarte Denise , Arnaldo Paulo , Enosse Sonia , Nogueira Fatima 
Published: May 2023

Abstract
Background
Malaria remains one of the most serious public health problems in sub-Saharan Africa and Mozambique is the world's fourth largest contributor, with 4.7% of disease cases and 3.6% of total deaths due to malaria. Its control relies on the fight against the vector and treatment of confirmed cases with anti-malarial drugs. Molecular surveillance is an important tool for monitoring the spread of anti-malarial drug resistance.

Methods
A cross-sectional study recruited 450 participants with malaria infection detected by Rapid Diagnostic Tests, from three different study sites (Niassa, Manica and Maputo) between April and August 2021. Correspondent blood samples were collected on filter paper (Whatman® FTA® cards), parasite DNA extracted and pfk13 gene sequenced using Sanger method. SIFT software (Sorting Intolerant From Tolerant) was used, predict whether an amino acid substitution affects protein function.

Results
No pfkelch13-mediated artemisinin resistance gene mutation was detected in this study settings. However, non-synonymous mutations were detected at prevalence of 10.2%, 6% and 5% in Niassa, Manica and Maputo, respectively. Most (56.3%) of the reported non-synonymous mutations were due to substitution at the first base of the codon, 25% at the second base and 18.8% at the third base. Additionally, 50% of non-synonymous mutations showed a SIFTscore bellow cut off value of 0.05, therefore, they were predicted to be deleterious.

Conclusion
These results do not show an emergence of artemisinin resistance cases in Mozambique. However, the increased number of novel non-synonymous mutations highlights the relevance of increasing the number of studies focused on the molecular surveillance of artemisinin resistance markers, for its early detection.
Artificial ovaries constructed from biodegradable chitin-based hydrogels with the ability to restore ovarian endocrine function and alleviate osteoporosis in ovariectomized mice
Authors: Xiang Du , Zhou Encheng , Wang Mei , Wang Kan , Zhou Shujun , Ma Qing , Zhong Zibiao , Ye Qifa , Chen Yun , Fan Xiaoli , Wang Yanfeng 
Published: May 2023

Abstract
Background
Artificial ovary (AO) is an alternative approach to provide physiological hormone to post-menopausal women. The therapeutic effects of AO constructed using alginate (ALG) hydrogels are limited by their low angiogenic potential, rigidity, and non-degradability. To address these limitations, biodegradable chitin-based (CTP) hydrogels that promote cell proliferation and vascularization were synthesized, as supportive matrix.

Methods
In vitro, follicles isolated from 10–12-days-old mice were cultured in 2D, ALG hydrogels, and CTP hydrogels. After 12 days of culture, follicle growth, steroid hormone levels, oocyte meiotic competence, and expression of folliculogenesis-related genes were monitored. Additionally, follicles isolated from 10–12-days-old mice were encapsulated in CTP and ALG hydrogels and transplanted into the peritoneal pockets of ovariectomised (OVX) mice. After transplantation, steroid hormone levels, body weight, rectal temperature, and visceral fat of the mice were monitored every two weeks. At 6 and 10 weeks after transplantation, the uterus, vagina, and femur were collected for histological examination.

Results
The follicles developed normally in CTP hydrogels under in vitro culture conditions. Additionally, follicular diametre and survival rate, oestrogen production, and expression of folliculogenesis-related genes were significantly higher than those in ALG hydrogels. After one week of transplantation, the numbers of CD34-positive vessels and Ki-67-positive cells in CTP hydrogels were significantly higher than those in ALG hydrogels (P < 0.05), and the follicle recovery rate was significantly higher in CTP hydrogels (28%) than in ALG hydrogels (17.2%) (P < 0.05). After two weeks of transplantation, OVX mice implanted with CTP grafts exhibited normal steroid hormone levels, which were maintained until week eight. After 10 weeks of transplantation, CTP grafts effectively ameliorated bone loss and atrophy of the reproductive organs, as well as prevented the increase in body weight and rectal temperature in OVX mice, which were superior to those elicited by ALG grafts.

Conclusions
Our study is the first to demonstrate that CTP hydrogels support follicles longer than ALG hydrogels in vitro and in vivo. The results highlight the clinical potential of AO constructed using CTP hydrogels in the treatment of menopausal symptoms.
Disease relapse rate in children with autoimmune rheumatic diseases after COVID-19 infection and vaccination
Authors: Šinkovec Savšek Tjaša , Zajc Avramovič Mojca , Avčin Tadej , Korva Miša , Avšič Županc Tatjana , Toplak Nataša 
Published: May 2023

Abstract
Background
Paediatric patients with autoimmune rheumatic diseases (pARD) are often immunocompromised because of the disease and/or the therapy they receive. At the beginning of COVID-19 pandemic there was a great concern about the possibility of severe SARS-CoV-2 infection in these patients. The best method of protection is vaccination, so as soon as vaccine was licenced, we aimed to vaccinate them. Data on disease relapse rate after COVID-19 infection and vaccination are scarce, but they play important role in everyday clinical decisions.

Methods
The aim of this study was to determine the relapse rate of autoimmune rheumatic disease (ARD) after COVID-19 infection and vaccination. Data on demographic, diagnosis, disease activity, therapy, clinical presentation of the infection and serology were collected from pARD who had COVID-19 and from pARD who were vaccinated against COVID-19, from March 2020 to April 2022. All vaccinated patients received two doses of the BNT162b2 BioNTech vaccine, on average, 3.7 (S.D.=1.4) weeks apart. Activity of the ARD was followed prospectively. Relapse was defined as a worsening of the ARD in a time frame of 8 weeks after infection or vaccination. For statistical analysis, Fisher’s exact test and Mann-Whitney U test were used.

Results
We collected data from 115 pARD, which we divided into two groups. We included 92 pARD after infection and 47 after vaccination, with 24 in both groups (they were infected before/after vaccination). In 92 pARD we registered 103 SARS-CoV-2 infections. Infection was asymptomatic in 14%, mild in 67% and moderate in 18%, 1% required hospitalization; 10% had a relapse of ARD after infection and 6% after vaccination. There was a trend towards higher disease relapse rate after infection compared to vaccination, but the difference was not statistically significant (p = 0.76). No statistically significant difference was detected in the relapse rate depending on the clinical presentation of the infection (p = 0.25) or the severity of the clinical presentation of COVID-19 between vaccinated and unvaccinated pARD (p = 0.31).

Conclusions
There is a trend towards a higher relapse rate in pARD after infection compared to vaccination and connection between the severity of COVID-19 and vaccination status is plausible. Our results were, however, not statistically significant.
Evaluation of optimal single-photon emission computed tomography reference value and three-dimensional mandibular growth pattern in 54 Chinese unilateral condylar hyperplasia patients
Authors: Ouyang Ningjuan , Zhang Chenglong , Xu Feng , Chen Tiantian , Shen Guofang , Si Jiawen , Yu Hongbo 
Published: May 2023

Abstract
Background
The research aimed to evaluate the optimal Single-Photon Emission Computed Tomography (SPECT) cut-off value in differentiating condylar growth activeness, to observe 3-dimensional (3D) mandibular growth pattern, and to explore the potential correlation between 3D measurement parameters and SPECT uptake ratios in Chinese unilateral condylar hyperplasia (UCH) patients.

Methods
Data of fifty-four Chinese UCH patients were analyzed retrospectively. All patients underwent SPECT within 1 month before or after the first CT examination (CT1); and received a second CT examination at least 12 months later (CT2). Data from CT scans were analyzed by comparing bilateral differences between CT1 and CT2. The sensitivity and specificity of SPECT were calculated by the receiver operating characteristic (ROC) curve. Pearson’s correlation analysis was performed to investigate whether the mandibular growth was correlated with SPECT value.

Results
SPECT had a sensitivity of 68.00% and a specificity of 72.41%, with an area under the ROC curve being 0.709. The optimal SPECT cut-off value for evaluating condylar activity has been determined to be 13%. In patients with an active growing condyle, there was a significant increase in Co-Gn and Co-Go, but not in Go-Gn, Go-MF, or MF-Gn. Pearson’s correlation analysis revealed no correlation between 3D measurement parameters and differences in relative condylar uptake ratios.

Conclusion
SPECT showed good diagnostic performance in UCH with the cut-off value of 13%. For those with an active growing condyle, the mandible grows diagonally and vertically, while the relative condylar uptake ratio was not directly related to mandibular growth.
Nonanatomic healing of the greater tuberosity after plating in proximal humeral fractures: a case control study
Authors: Sheng Ning , Shi Tingwang , Wang Qiuke , Wang Lei , Chen Yunfeng 
Published: May 2023

Abstract
Background
Open reduction and plate internal fixation (ORIF) is one of the most common treatment methods for proximal humeral fractures. Complications associated with the greater tuberosity (GT) are rarely reported, therefore, the purpose of this study was to analyze the complications associated with the GT and the risk factors after locked-plate internal fixation.

Methods
We retrospectively analyzed the medical and radiographic data of patients with proximal humeral fractures involving the GT treated with locking plates between January 2016 and July 2019. We divided all patients into two groups, the anatomic GT healing group and the nonanatomic GT healing group, depending on the radiographic outcomes of the GT. Clinical outcome was assessed by the Constant scoring system. Potential risk factors included preoperative and intraoperative factors. Preoperative factors included sex, age, body mass index, fracture type, fracture-dislocation, proximal humeral bone mineral density, humeral head extension, hinge integrity, comminuted GT, volume and surface area of the main GT fragment, and displacement of the main GT fragment. Intraoperative factors were adequate medial support, residual head-shaft displacement, head-shaft angle and residual GT displacement. Univariate logistic regression and multivariate logistic regression were used to identify risk factors.

Results
There were 207 patients (130 women and 77 men; mean age, 55 years). GT anatomic healing was observed in 139 (67.1%) patients and nonanatomic healing in 68 (32.9%). Patients with GT nonanatomic healing had significantly inferior Constant scores than those with GT anatomic healing (75.0 ± 13.9 vs. 83.9 ± 11.8, P < 0.001). Patients with high GT malposition had worse Constant scores than patients with low GT malposition (73.3 ± 12.7 vs. 81.1 ± 11.4, P = 0.039). The multivariate logistic model showed that GT fracture characteristics were not risk factors for nonanatomic GT healing, while residual GT displacement was.

Conclusions
Nonanatomic healing of the GT is a high-rate complication of proximal humeral fractures, resulting in inferior clinical outcomes, especially for high GT malposition. Fracture characteristics of the GT are not risk factors for GT nonanatomic healing and GT comminution should not be regarded as a contraindication to ORIF for proximal humeral fractures.
Review on risk factors, classification, and treatment of sternal wound infection
Authors: Song Yaoyao , Chu Wanli , Sun Jiachen , Liu Xinzhu , Zhu Hongjuan , Yu Hongli , Shen Chuan’an 
Published: May 2023

AbstractSternal wound infection (SWI) is the most common complication of the median sternal incision. The treatment time is long, and the reconstruction is difficult, which causes challenges for surgeons. Plastic surgeons were often involved too late in such clinical scenarios when previous empirical treatments failed and the wound damage was relatively serious. Accurate diagnosis and risk factors against sternal wound infection need to be in focus. Classification of different types of sternotomy complications post-cardiac surgery is important for specific categorization and management. Not familiar with this kind of special and complex wound, objectively increasing the difficulty of wound reconstruction. The purpose of this comprehensive review is to review the literature, introduce various SWI risk factors related to wound nonunion, various classification characteristics, advantages and disadvantages of various wound reconstruction strategies, to help clinicians understand the pathophysiological characteristics of the disease and choose a better treatment method.
Fatigue in patients with syndromic heritable thoracic aortic disease: a systematic review of the literature and a qualitative study of patients’ experiences and perceptions
Authors: Velvin Gry , Johansen Heidi , Østertun-Geirdal Amy , Bathen Trine 
Published: May 2023

AbstractIntroductionThe purpose of this study was to explore the literature on fatigue in patients with syndromic heritable thoracic aortic disease (sHTAD), including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), vascular Ehlers Danlos syndrome (vEDS) and other sHTADs, critically appraise and synthesize the relevant literature. We also aimed to investigate how adults with sHTAD experience and perceive fatigue, and to discuss clinical implications and direction for further research.MethodsFirst, a systematic review was performed by searching the published literature in all relevant databases and other sources until 20th October 2022. Second, a qualitative focus group interview study was conducted of 36 adults with sHTADs (LDS n = 11, MFS n = 14, vEDS n = 11).ResultsIn the systematic review, 33 articles satisfied the eligibility criteria (3 reviews and 30 primary studies). Of the primary studies: 25 dealt with adults (MFS n = 17, MFS/EDS n = 1, EDS n = 2, LDS/vEDS n = 3, different sHTADs n = 2), 5 with children (MFS n = 4, different sHTADs n = 1). Twenty-two were cross-sectional quantitative studies, 4 prospective and 4 qualitative studies. The quality of the included studies was mostly good, but many had small sample sizes, low response rates and/or participants without verified diagnosis. Despite these limitations, studies indicated high prevalence of fatigue (ranging from 37 to 89%), and fatigue was associated with both health and psychosocial aspects. Few studies found that fatigue was associated with disease-related symptoms. In the qualitative focus groups most of the participants reported that they had experienced fatigue which influenced several aspects of life. Four themes related to fatigue were elucidated: (1) different diagnoses–different fatigue?, (2) the nature of fatigue, (3) searches for causes of fatigue, (4) dealing with fatigue in daily life. The four themes seemed mutually interrelated in terms of barriers, strategies and facilitators for dealing with fatigue. The participants experienced fatigue as a consistent dilemma between self-assertion and inadequacy. Fatigue seems to influence several aspects of daily life and may be one of the most debilitating symptoms of having a sHTAD.ConclusionFatigue seems to negatively impact the lives of people with sHTADs and should be recognized as an important aspect in the lifelong follow-up of these patients. The life-threatening complications of sHTADs may result in emotional stress, including fatigue and the risk of developing a sedentary lifestyle. Research and clinical initiatives should consider rehabilitation interventions aiming at postponing the onset or reducing symptoms of fatigue.
A short-term bioreactor assay to assess the effect of essential oils on a microbiota derived from piglet’s intestinal content
Authors: Bellerose Mathieu , Fravalo Philippe , Mainville Isabelle , Arcand Yves , Thibodeau Alexandre 
Published: May 2023

Abstract
Background
Modulating the microbiota is an emerging way to improve pig health. In-vitro bioreactor systems can be used to reproduce intestinal microbiota to study modulating avenues. In this study, a continuous feeding system to support a microbiota derived from piglet colonic contents, over 72 h, was developed. The microbiota from piglets was collected and used as inoculum. The culture media was derived from an artificial digestion of piglet feed. The microbiota diversity in time, the reproducibility between replicates and the diversity of the bioreactor microbiota compared to the inoculum was assessed. Essential oils were used as a proof of concept to assess the in vitro microbiota modulation. The microbiota diversity was assessed by 16S rRNA amplicon sequencing. Quantitative PCR was also used for total bacteria, lactobacilli and Enterobacteria.

Results
At the start of the assay, the bioreactor microbiota diversity was similar to the inoculum. Time and replication affected the bioreactor microbiota diversity. Between 48 and 72 h, no statistical variation of the microbiota diversity was observable. After a 48 h running period, thymol and carvacrol were added at 200 ppm or 1000 ppm for 24 h. No microbiota modification was observed by sequencing. Quantitative PCR results showed a significant growth of lactobacilli when thymol was used at 1000 ppm, where only a trend was observed with the 16S analysis.

Conclusions
This study presents a bioreactor assay that can be used as a tool for rapid screening of additives and suggests that the effects of essential oils on the microbiota are subtle, acting against a few bacterial genera.
Comparison of two doses of leucovorin in severe low-dose methotrexate toxicity – a randomized controlled trial
Authors: Bhargava Mudit , Kopp Chirag Rajkumar , Naidu Shankar , Dhibar Deba Prasad , Saroch Atul , Khadwal Alka , Narang Tarun , Jain Siddharth , Khullar Aastha , Leishangthem Bidya , Sharma Aman , Kumar Susheel , Sharma Shefali , Jain Sanjay , Dhir Varun 
Published: May 2023

Abstract
Background
Leucovorin (folinic acid) is a commonly used antidote for severe toxicity with low-dose methotrexate, but its optimum dose is unclear, varying from 15 to 25 mg every 6-h.

Methods
Open-label RCT included patients with severe low-dose (≤ 50 mg/week) methotrexate toxicity defined as WBC ≤ 2 × 10^9/L or platelet ≤ 50 × 10^9/L and randomized them to receive either usual (15 mg) or high-dose (25 mg) intravenous leucovorin given every 6-h. Primary outcome was mortality at 30-days and secondary outcomes were hematological recovery and mucositis recovery. Trial Registration number: CTRI/2019/09/021152.

Results
Thirty-eight patients were included, most with underlying RA who had inadvertently overdosed MTX (taken daily instead of weekly). At randomization, the median white blood and platelet count were 0.8 × 10^9/L and 23.5 × 10^9/L. 19 patients each were randomized to receive either usual or high-dose leucovorin. Number (%) of deaths over 30-days was 8 (42) and 9 (47) in usual and high-dose leucovorin groups (Odds ratio 1.2, 95% CI 0.3 to 4.5, p = 0.74). On Kaplan–Meier, there was no significant difference in survival between the groups (hazard ratio 1.1, 95% CI 0.4 to 2.9, p = 0.84). On multivariable cox-regression, serum albumin was the only predictor of survival (hazard ratio 0.3, 95% CI 0.1 to 0.9, p = 0.02). There was no significant difference in hematological or mucositis recovery between the two groups.

Conclusion
There was no significant difference in survival or time-to hematological recovery between the two doses of leucovorin. Severe low-dose methotrexate toxicity carried a significant mortality.