bluuebunny/crossref_metadata_2025 huggingface dataset:
Early contribution of germline and nevi genetic alterations to a rapidly-progressing cutaneous melanoma patient: a case report
Authors: Mordoh Ana , Triviño Pardo Juan Carlos , Carri Ibel , Barrio María Marcela , Mordoh José , Aris Mariana
Published: January 2023

Background

Cutaneous melanoma is the skin cancer with the highest mutational burden and metastatic rate. Early genetic alterations and biomarkers of distant progression are a point of interest. In addition to germline-susceptibility loci, almost 30% of melanomas arise from precursor benign nevi lesions, providing a source for malignant transformation.

Case presentation

Patient#009 developed a cutaneous melanoma over a nevus, followed by progression to regional and distant metastases in months, unresponsive to targeted therapy. To search for the genetic contribution to this rapid progression, a longitudinal analysis was performed through WES of germline, nevi, primary tumor, and a metastatic lymph node. Differential SNP/INDEL and CNV gene alterations, with functional impact on key pathways and cancer hallmarks in each step of evolution, were discerned. Tumor-associated nevus was, for the first time, split into two sections, distant and adjacent to the primary tumor, to study its heterogeneity.

Shared SNP alterations, with stable allele fraction from germline to metastasis were detected, mainly affecting DNA repair genes and promoting genome instability. Early somatic alterations, shared by nevi and primary and metastatic tumors, included BRAFV600Eand focal copy-loss of several genes, acquiring additional cancer hallmarks. Phylogenetic analyses revealed that these common somatic alterations would provide a “bridge”, allowing progression from a benign to a malignant state. Distant and adjacent nevi were rich in alterations, presenting differential SNP and CNV alterations. Upon tumor transformation, a marked increase in CNV over SNP alterations was determined. Both the number of SNP and CNV-affected genes, including known driver genes, increased throughout progression, although TMB levels remained lower than expected for melanoma. Typical alterations in BRAFV600Etumors related to intrinsic resistance to targeted therapy were found, including BRAF amplification and loss of PTEN, CDKN2A/B, and TP53 surveillance genes. Finally, numerous metastatic alterations were detected, further promoting tumor progression.

Conclusions

In this patient, longitudinal WES analysis revealed a sequential and cumulative pattern of genetic alterations, where germline and nevi somatic events contributed early to its rapid clinical progression. In this case report, we found tumor-associated nevi as genetically heterogeneous precursor entities, in which potential prognostic biomarkers should be studied prospectively.
In ‘real world’ patients with COPD, exacerbation history, and not blood eosinophils, is the most reliable predictor of future exacerbations
Authors: Worth Heinrich , Buhl Roland , Criée Carl-Peter , Kardos Peter , Gückel Eva , Vogelmeier Claus F.
Published: January 2023

Introduction

There is an interest in the role of blood eosinophils for predicting inhaled corticosteroid (ICS) response in chronic obstructive pulmonary disease (COPD). Most data are from interventional clinical studies; data from unselected real-world populations may help better inform treatment decisions. DACCORD is a non-interventional real-world study. Cohort 3 recruited patients with COPD who had received triple therapy for ≥ 6 months; prior to entry patients either continued triple therapy, or switched to a long-acting muscarinic antagonist/long-acting beta2-agonist (LABA/LAMA), and were followed for 12 months.

Methods

For these post-hoc analyses, patients were divided into four groups based on exacerbation history and baseline blood eosinophil count (< 100 vs. > 300 cells/µL). Exacerbation rates were calculated overall and for the two treatments.

Results

Among the 430 patients in the current analyses, the largest groups had low exacerbation history with high (44.2%) or low eosinophils (36.7%). Most patients did not exacerbate during follow-up (68.8% overall; 83.2% and 63.7% with LABA/LAMA and triple therapy). The highest exacerbation rates were in groups with high exacerbation history, differing significantly in the overall analyses from those with low exacerbation history (matched by eosinophil count); rates did not differ when grouped by eosinophil count (matched by exacerbation history).

Conclusions

Although most patients in these analyses did not exacerbate during follow-up, whereas exacerbation history is a predictor of future exacerbations, blood eosinophil count is not. This suggests that although eosinophil count may help to guide ICS initiation, this is less of a consideration when ‘stepping-down’ from triple therapy to a LABA/LAMA
Combination therapy with oncolytic viruses and immune checkpoint inhibitors in head and neck squamous cell carcinomas: an approach of complementary advantages
Authors: Dong Hui , Li Mengli , Yang Chen , Wei Wei , He Xianglei , Cheng Gang , Wang Shibing
Published: January 2023

Squamous cell carcinomas are the most common head and neck malignancies. Significant progress has been made in standard therapeutic methods combining surgery, radiation, and chemotherapy. Nevertheless, the 5-year survival rate remains at 40–50%. Immune checkpoint inhibitors (ICIs) are a new strategy for treating head and neck squamous cell carcinomas (HNSCCs). Still, the overall response and effective rates are poor, as HNSCCs are ‘cold’ tumors with an immunosuppressive tumor microenvironment (TME), limiting ICI’s beneficial effects. In this case, transforming the tumor suppression microenvironment before using ICIs could be helpful. Oncolytic viruses (OVs) can transform cold tumors into hot tumors, improving the situation. Talimogene laherparepvec (T-VEC), oncolytic immunotherapy authorized for advanced melanoma, also showed good safety and antitumor activity in treating head and neck cancer and pancreatic cancer. In combination with pembrolizumab, T-Vec may have more anticancer efficacy than either drug alone. Therefore, understanding the mechanisms underpinning OVs and their potential synergism with ICIs could benefit patients with HNSCC.
Genetic variations in human ATP2B4 gene alter Plasmodium falciparum in vitro growth in RBCs from Gambian adults
Authors: Joof Fatou , Hartmann Elena , Jarvis Alison , Colley Alhassan , Cross James H. , Avril Marion , Prentice Andrew M. , Cerami Carla
Published: January 2023

Background

Polymorphisms inATP2B4coding for PMCA4b, the primary regulator of erythrocyte calcium concentration, have been shown by GWAS and cross-sectional studies to protect against severe malaria but the mechanism remains unknown.

Methods

Using a recall-by-genotype design, we investigated the impact of a common haplotype variant inATP2B4using in vitro assays that model erythrocyte stage malaria pathogenesis. Ninety-six donors representing homozygotes (carriers of the minor alleles, T/T (variant), heterozygote T/C and wildtype C/C (ancestral)) carriers of the tagging SNP rs1541252 were selected from a cohort of over 12,000 participants in the Keneba Biobank.

Results

Red blood cells (RBCs) from homozygotes showed reduced PMCA4b protein expression (mean fluorescence intensities (MFI = 2428 ± 124, 3544 ± 159 and 4261 ± 283], for homozygotes, heterozygotes and wildtypes respectively, p < 0.0001) and slower rates of calcium expulsion (calcium t½ ± SD = 4.7 ± 0.5, 1.8 ± 0.3 and 1.9 ± 0.4 min, p < 0.0001). Growth of aPlasmodium falciparumlaboratory strain (FCR3) and two Gambian field isolates was decreased in RBCs from homozygotes compared to heterozygotes and wildtypes (p < 0.01). Genotype group did not affect parasite adhesion in vitro orvar-gene expression in malaria-infected RBCs. Parasite growth was inhibited by a known inhibitor of PMCA4b, aurintricarboxylic acid (IC50 = 122uM CI: 110–134) confirming its sensitivity to calcium channel blockade.

Conclusion

The data support the hypothesis that thisATP2B4genotype, common in The Gambia and other malaria-endemic areas, protects against severe malaria through the suppression of parasitaemia during an infection. Reduction in parasite density plays a pivotal role in disease outcome by minimizing all aspects of malaria pathogenesis. Follow up studies are needed to further elucidate the mechanism of protection and to determine if thisATP2B4genotype carries a fitness cost or increases susceptibility to other human disease.
Why are they “unreached”? Macro and Meso determinants of health care access in hard to reach areas of Odisha, India
Authors: Nallala Srinivas , Ghosh Upasona , Desaraju Shyama Sundari , Kadam Shridhar , Kadarpeta Rahul Reddy , Van Belle Sara
Published: January 2023

Background

Reaching hard to reach populations is key to reduce health inequities. Despite targeted interventions, status of crucial public health indicators like neonatal and maternal mortality is still far from optimal. Complex interplay of social determinants can influence both communities and health care workers to effectively access each other. We argue that culturally sensitive and contextually relevant healthcare provision has potential to increase health care utilization by the vulnerable communities living in remote areas.

Methods

The study is an exploratory case study using rapid ethnographic techniques to understand the interplay of social determinants in hard to reach areas of Odisha state, India. We used in-depth interviews, focus group discussion, participatory action research and key informant interviews as tools for data collection. The analysis of data has been guided by thematic analysis approach.

Results

We found that there are further layers within the designated hard to reach areas and those can be designated as-i) extremely remote ii) remote and iii) reachable areas. Degree of geographic difficulties and cultural dynamics are deciding the ‘perceived’ isolation and interaction with health care providers in hard to reach areas. This ultimately leads to impacting the utilization of the facilities. At extremely remote areas, felt health needs are mainly fulfilled by traditional healers and ethno-medical practices. In reachable areas, people are more prone to seek care from the public health facilities because of easy accessibility and outreach. Being in middle people in remote areas, diversify health care seeking depending upon social (e.g. patient’s gender) economic (e.g. avoid catastrophic expenditure) and health system (timely availability of health human resources, language barriers) factors.

Conclusion

Our research highlights the need to value and appreciate different worldviews, beliefs and practices, and their understanding of and engagement with the pluralistic health care system around them. Other than pursuing the ‘mainstreaming’ of a standardized health system model across hard to reach areas, strategies need to be adaptive as per local factors. To handle that existing policies need revision with a focus on culturally sensitive and contextual care provision.
NAMPT encapsulated by extracellular vesicles from young adipose-derived mesenchymal stem cells treated tendinopathy in a “One-Stone-Two-Birds” manner
Authors: Wu Guanghao , Su Qihang , Li Jie , Xue Chao , Zhu Jie , Cai Qiuchen , Huang Jingbiao , Ji Shaoyang , Cheng Biao , Ge Hengan
Published: January 2023

Background

Tendinopathy is the leading sports-related injury and will cause severe weakness and tenderness. Effective therapy for tendinopathy remains limited, and extracellular vesicles (EVs) derived from adipose tissue-derived mesenchymal stem cells (ADMSCs) have demonstrated great potential in tendinopathy treatment; however, the influence of aging status on EV treatment has not been previously described.

Results

In this study, it was found that ADMSCs derived from old mice (ADMSCold) demonstrated remarkable cellular senescence and impaired NAD+ metabolism compared with ADMSCs derived from young mice (ADMSCyoung). Lower NAMPT contents were detected in both ADMSCold and its secreted EVs (ADMSCold-EVs). Advanced animal experiments demonstrated that ADMSCyoung-EVs, but not ADMSCold-EVs, alleviated the pathological structural, functional and biomechanical properties in tendinopathy mice. Mechanistic analyses demonstrated that ADMSCyoung-EVs improved cell viability and relieved cellular senescence of tenocytes through the NAMPT/SIRT1/PPARγ/PGC-1α pathway. ADMSCyoung-EVs, but not ADMSCold-EVs, promoted phagocytosis and M2 polarization in macrophages through the NAMPT/SIRT1/Nf-κb p65/NLRP3 pathway. The macrophage/tenocyte crosstalk in tendinopathy was influenced by ADMSCyoung-EV treatment and thus it demonstrated "One-Stone-Two-Birds" effects in tendinopathy treatment.

Conclusions

This study demonstrates an effective novel therapy for tendinopathy and uncovers the influence of donor age on curative effects by clarifying the detailed biological mechanism.

Graphical Abstract
Breastfeeding, socioeconomic status, and long-term postpartum weight retention
Authors: Foster Saralyn F. , Vazquez Christian , Cubbin Catherine , Nichols Amy R. , Rickman Rachel R. , Widen Elizabeth M.
Published: January 2023

Background

Almost half of all pregnant women in the United States gain weight above Institute of Medicine gestational weight gain guidelines. Breastfeeding has been shown to reduce weight retention in the first year postpartum; however, women with lower socioeconomic status (SES) tend to initiate breastfeeding less often than women with higher SES. We investigated associations between duration of breastfeeding with mother’s long-term postpartum weight status at 4–10 years and evaluated whether the associations varied by SES.

Methods

Maternal and infant dyads (N = 2144 dyads) are from the Geographic Research on Wellbeing survey (GROW), 2012–2013, a long-term, cross-sectional follow-up of the Maternal and Infant Health Assessment (MIHA) based in California, USA. Pre-pregnancy body mass index (BMI) was obtained from self-report of height and weight during MIHA, while breastfeeding history and self-report of current body weight was collected at the 4–10 year GROW postpartum visit. SES score was derived from a composite score of percent federal poverty level and education and was dichotomized into High and Low SES groups at a score of three. Multivariable linear regression was used to examine association between breastfeeding and maternal weight status, and to examine for effect modification by SES.

Results

Average long-term weight retention 4–10 years postpartum was 4.0 kg. Fewer lower SES vs. higher SES women breast fed at least six months (51% versus 70%, p < .001) or ever breastfed (74% versus 89%, P < .001). Women who breastfed at least six months had lower long-term postpartum weight retention compared to those who did not (b = -1.06 kg, (-1.93, 0.25); p = 0.01); however, these association did not vary by SES.

Conclusion

Six months of breastfeeding is associated with lower BMI at 4–10 years and lower body weight, and effects do not vary by SES. Future policies and guidelines should consider building an infrastructure that is supportive of longer breastfeeding duration. Moreover, further research is needed to identify the impact of additional behavioral and environmental factors on long-term maternal weight status. Understanding the drivers of excessive weight retention pospartum can help us not only improve the pregnant person’s health but the health of their children.
Dosimetric comparison of deformable image registration and synthetic CT generation based on CBCT images for organs at risk in cervical cancer radiotherapy
Authors: Chang Yankui , Liang Yongguang , Yang Bo , Qiu Jie , Pei Xi , Xu Xie George
Published: January 2023

Objective

Anatomical variations existing in cervical cancer radiotherapy treatment can be monitored by cone-beam computed tomography (CBCT) images. Deformable image registration (DIR) from planning CT (pCT) to CBCT images and synthetic CT (sCT) image generation based on CBCT are two methods for improving the quality of CBCT images. This study aims to compare the accuracy of these two approaches geometrically and dosimetrically in cervical cancer radiotherapy.

Methods

In this study, 40 paired pCT-CBCT images were collected to evaluate the accuracy of DIR and sCT generation. The DIR method was based on a 3D multistage registration network that was trained with 150 paired pCT-CBCT images, and the sCT generation method was performed based on a 2D cycle-consistent adversarial network (CycleGAN) with 6000 paired pCT-CBCT slices for training. Then, the doses were recalculated with the CBCT, pCT, deformed pCT (dpCT) and sCT images by a GPU-based Monte Carlo dose code, ArcherQA, to obtain DoseCBCT, DosepCT, DosedpCT and DosesCT. Organs at risk (OARs) included small intestine, rectum, bladder, spinal cord, femoral heads and bone marrow, CBCT and pCT contours were delineated manually, dpCT contours were propagated through deformation vector fields, sCT contours were auto-segmented and corrected manually.

Results

The global gamma pass rate of DosesCT and DosedpCT was 99.66% ± 0.34%, while that of DoseCBCT and DosedpCT was 85.92% ± 7.56% at the 1%/1 mm criterion and a low-dose threshold of 10%. Based on DosedpCT as uniform dose distribution, there were comparable errors in femoral heads and bone marrow for the dpCT and sCT contours compared with CBCT contours, while sCT contours had lower errors in small intestine, rectum, bladder and spinal cord, especially for those with large volume difference of pCT and CBCT.

Conclusions

For cervical cancer radiotherapy, the DIR method and sCT generation could produce similar precise dose distributions, but sCT contours had higher accuracy when the difference in planning CT and CBCT was large.
Clinical effects of early debridement, internal fixation, and Masquelet technique for childhood chronic haematogenous osteomyelitis of long bones
Authors: Shi Jian , Yang Xiaoyong , Song Muguo , Zhang Xijiao , Xu Yongqing
Published: January 2023

Background

Childhood chronic haematogenous osteomyelitis (CCHOM) is a severe condition in paediatric patients. The optimal timing of debridement and the subsequent method of bone reconstruction in CCHOM patients remain controversial. The purpose of this study was to assess the treatment efficacy of Masquelet technique with early debridement and internal fixation in CCHOM of long bones.

Methods

Between January 2016 and January 2021, a total of 21 patients (18 males, 3 females) with CCHOM of long bone were included. The mean age was 10.4 years (range, 2–18 years). All cases were treated by a two-stage surgical protocol of Masquelet technique. In the first stage, aggressive debridement, sequestrectomy, and inducing membrane by bone cement spacer were performed after definite diagnosis. In the second stage, cement spacer was removed, and autologous and allogeneic bone was grafted. Internal fixation was used for the first and/or second stage depending on stability requirements. The patients’ clinical and imaging results were retrospectively analysed.

Results

The mean follow-up was 31.7 months (range, 21–61 months). None of the patients experienced recurrence of infection. Radiographic bone union time was 4.3 months (range, 2.5–11 months). Five cases underwent re-operation due to complications such as bone resorption or refracture. By the last follow-up visit, bones had healed and all of the patients had resumed daily living and sports activities.

Conclusion

The Masquelet technique with early debridement and internal fixation is a viable surgical method for the management of large long bone defects of CCHOM patients.
Temporal pain processing in the primary somatosensory cortex and anterior cingulate cortex
Authors: Sun Guanghao , McCartin Michael , Liu Weizhuo , Zhang Qiaosheng , Kenefati George , Chen Zhe Sage , Wang Jing
Published: January 2023

Pain is known to have sensory and affective components. The sensory pain component is encoded by neurons in the primary somatosensory cortex (S1), whereas the emotional or affective pain experience is in large part processed by neural activities in the anterior cingulate cortex (ACC). The timing of how a mechanical or thermal noxious stimulus triggers activation of peripheral pain fibers is well-known. However, the temporal processing of nociceptive inputs in the cortex remains little studied. Here, we took two approaches to examine how nociceptive inputs are processed by the S1 and ACC. We simultaneously recorded local field potentials in both regions, during the application of a brain-computer interface (BCI). First, we compared event related potentials in the S1 and ACC. Next, we used an algorithmic pain decoder enabled by machine-learning to detect the onset of pain which was used during the implementation of the BCI to automatically treat pain. We found that whereas mechanical pain triggered neural activity changes first in the S1, the S1 and ACC processed thermal pain with a reasonably similar time course. These results indicate that the temporal processing of nociceptive information in different regions of the cortex is likely important for the overall pain experience.
The development of a cSMART-based integrated model for hepatocellular carcinoma diagnosis
Authors: Wu Tong , Fan Rong , Bai Jian , Yang Zhao , Qian Yun-Song , Du Lu-Tao , Wang Chun-Ying , Wang Ying-Chao , Jiang Guo-Qing , Zheng Dan , Fan Xiao-Tang , Zheng Bo , Liu Jing-Feng , Deng Guo-Hong , Shen Feng , Hu He-Ping , Ye Yi-Nong , Zhang Qing-Zheng , Zhang Jing , Gao Yan-Hang , Xia Jie , Yan Hua-Dong , Liang Min-Feng , Yu Yan-Long , Sun Fu-Ming , Gao Yu-Jing , Sun Jian , Zhong Chun-Xiu , Wang Yin , Wang Hui , Kong Fei , Chen Jin-Ming , Wen Hao , Wu Bo-Ming , Wang Chuan-Xin , Wu Lin , Hou Jin-Lin , Liu Xiao-Long , Wang Hong-Yang , Chen Lei
Published: January 2023

Background

Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising.

Methods

Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes.

Results

An integrated diagnostic model called “Combined method” was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.
Patterns of toxicity burden for FDA-approved immune checkpoint inhibitors in the United States
Authors: Yang Fan , Shay Chloe , Abousaud Marin , Tang Chris , Li Yamin , Qin Zhaohui , Saba Nabil F. , Teng Yong
Published: January 2023

Background

Immune-related adverse events (irAEs) are a common phenomenon in cancer patients treated with immune checkpoint inhibitors (ICIs). Surprisingly, the toxicity burdens of these irAEs have not been illustrated clearly. In this study, we analyzed irAEs for seven FDA-approved ICIs in cancer treatment to show the pattern of toxicity burden among cancer patients.

Methods

irAEs associated with seven FDA-approved ICIs, including three PD-1 inhibitors (cemiplimab, nivolumab and pembrolizumab), three PD-L1 inhibitors (atezolizumab, avelumab and durvalumab), and one CTLA-4 inhibitor (ipilimumab), were analyzed based on data from 149,303 reported cases (from January 1, 2015 to June 30, 2022) collected from the FDA Adverse Events Reporting System (FAERS) public dashboard. Proportions of serious irAEs and correlations with tumor type, age and sex were assessed via R package and GraphPad software.

Results

irAEs related to anti-PD-1 ICIs required less hospital care resources compared with anti-PD-L1 and anti-CTLA-4 ICIs. Patients treated with pembrolizumab had relatively fewer serious cases. Treatment with ICIs led to the highest probability of serious irAEs in patients with lung cancer. ‘Respiratory, thoracic and mediastinal disorders’ and ‘gastrointestinal disorders’ were the two most common groups of disorders caused by the seven ICIs studied. ‘Cardiac disorders’ was the main type of disorders caused by these ICIs in cancer patients aged 65–85, while ‘reproductive system and breast disease’ was the main type of disorder in cancer patients aged 18–64. ‘Respiratory, thoracic, mediastinal diseases’ and ‘reproductive system and breast diseases’ were the main types of disorders associated with treatment with these ICIs in male and female patients, respectively.

Conclusion

Tissue and organ toxicities of ICIs are age and sex specific. There are risks of respiratory and urinary system toxicity in male patients and reproductive system toxicity in female patients treated with the ICIs studied. Future studies on the toxicity burden of ICIs should incorporate age and sex differences to better understand the relevance of ICI toxicity burden to human immune function to develop appropriate tumor immune and therapeutic intervention strategies.
First record of Trypanosoma evansi DNA in Dichelacera alcicornis and Dichelacera januarii (Diptera: Tabanidae) flies in South America
Authors: Ramos Carlos José Raupp , de Souza Franco Cintia , da Luz Sabrina Pogere , Marques Júlia , de Souza Ketriane Mota , do Nascimento Luiz Flávio Nepomuceno , das Neves Gabriella Bassi , Moreira Renato Simões , Miletti Luiz Claudio
Published: January 2023

Background

Trypanosoma evansi infects a large number of wild and domestic animals and causes a spoliative disease known as surra. It is mechanically transmitted, mainly by biting flies of the genera Tabanus and Stomoxys. The detection of T. evansi DNA in the feeding apparatus of Dichelacera alcicornis and Dichelacera januarii from South America is reported, to the best of our knowledge, for the first time.

Methods

Tabanids were collected weekly from February 2018 to February 2019 from two sites. The feeding apparatus was removed and DNA extraction, polymerase chain reaction and sequencing were performed.

Results

A 205-base pair fragment of the variant surface protein RoTat 1.2 gene, confirmed by DNA sequencing, was amplified from the feeding apparatus of D. alcicornis and D. januarii.

Conclusions

This is, to the best of our knowledge, the first record of T. evansi DNA in South American tabanids.

Graphical abstract
Phylogenetic evidence for a clade of tick-associated trypanosomes
Authors: Koual Rachid , Buysse Marie , Grillet Justine , Binetruy Florian , Ouass Sofian , Sprong Hein , Duhayon Maxime , Boulanger Nathalie , Jourdain Frédéric , Alafaci Aurélien , Verdon Julien , Verheyden Hélène , Rispe Claude , Plantard Olivier , Duron Olivier
Published: January 2023

Background

Trypanosomes are protozoan parasites of vertebrates that are of medical and veterinary concern. A variety of blood-feeding invertebrates have been identified as vectors, but the role of ticks in trypanosome transmission remains unclear.

Methods

In this study, we undertook extensive molecular screening for the presence and genetic diversity of trypanosomes in field ticks.

Results

Examination of 1089 specimens belonging to 28 tick species from Europe and South America led to the identification of two new trypanosome strains. The prevalence may be as high as 4% in tick species such as the castor bean tick Ixodes ricinus, but we found no evidence of transovarial transmission. Further phylogenetic analyses based on 18S rRNA, EF1-α, hsp60 and hsp85 gene sequences revealed that different tick species, originating from different continents, often harbour phylogenetically related trypanosome strains and species. Most tick-associated trypanosomes cluster in a monophyletic clade, the Trypanosoma pestanai clade, distinct from clades of trypanosomes associated with transmission by other blood-feeding invertebrates.

Conclusions

These observations suggest that ticks may be specific arthropod hosts for trypanosomes of the T. pestanai clade. Phylogenetic analyses provide further evidence that ticks may transmit these trypanosomes to a diversity of mammal species (including placental and marsupial species) on most continents.

Graphical Abstract
Does higher knee hyperextension in patients with hemiplegia affect lateral and medial meniscus volume in the paretic leg? A cross-sectional study
Authors: Li Wenshan , Li Tiancong , Xi Xiaoshuang , Zhang Rong , Sun Weishuang , Zhang Dan , Gong Weijun
Published: January 2023

Background

After stroke, an abnormal gait pattern gradually leads to knee pain and joint lesions, resulting the gait instability. However, the correlation between the knee hyperextension and gait pattern, the meniscus volume, and the water content of meniscus in paretic and non-paretic legs has not been fully investigated. Moreover, most of physicians tend to ignore this knee hyperextension. This study attempted to emphasize the importance of knee hyperextension using gait analysis and Magnetic resonance imaging (Trial registration number ChiCTR2000039641, date of registration 04/11/2020).

Methods

Eight patients with chronic hemiplegic (6 male, 2 female) volunteered to participate in this study. Participants was recruited if they had a hemiplegia following a stroke occurring more than 6 months, had an ability to walk 10 m without aids, had a Function Ambulation Category level at least 3 and above, and had a hemiplegic lower extremity identified as Brunnstrom state III or above identification. The spatial–temporal gait parameters and kinematic parameters in the paretic and the non-paretic legs and the percentage of free water content in deep and shallow layers.

Results

Longer time since hemiplegia led to larger angles of knee hyperextension (R = 0.56, p = 0.016), larger angles of knee hyperextension led to more tears in meniscus (R =  − 0.53, − 0,57 and − 0.70), and larger angles of knee hyperextension decreased water content of the lateral meniscus in the non-paretic leg (R =  − 0.91) but increased water content of the medial meniscus (R = 0.53 and 0.63).

Conclusions

The knee hyperextension could not be ignored by physicians and needed to be diagnosed and treated as early as possible, the time since hemiplegia could be an indicator of sign of knee hyperextension.
Altered metabolic connectivity within the limbic cortico-striato-thalamo-cortical circuit in presymptomatic and symptomatic behavioral variant frontotemporal dementia
Authors: Liu Li , Chu Min , Nie Binbin , Jiang Deming , Xie Kexin , Cui Yue , Liu Lin , Kong Yu , Chen Zhongyun , Nan Haitian , Rosa-Neto Pedro , Wu Liyong
Published: January 2023

Background

Behavioral variant frontotemporal dementia (bvFTD) is predominantly considered a dysfunction in cortico-cortical transmission, with limited direct investigation of cortical-subcortical transmission. Thus, we aimed to characterize the metabolic connectivity between areas of the limbic cortico-striato-thalamic-cortical (CSTC) circuit in presymptomatic and symptomatic bvFTD patients.

Methods

Thirty-three bvFTD patients and 33 unrelated healthy controls were recruited for this study. Additionally, six asymptomatic carriers of the MAPT P301L mutation were compared with 12 non-carriers who were all from the same family of bvFTD. Each participant underwent neuropsychological assessment, genetic testing, and a hybrid PET/MRI scan. Seed-based metabolic connectivity based on [18F]-fluorodeoxyglucose PET between the main components within the limbic CSTC circuit was explored according to the Oxford-GSK-Imanova Striatal Connectivity Atlas.

Results

BvFTD patients exhibited reduced metabolic connectivity between the relays in the limbic CSTC circuit, which included the frontal region (ventromedial prefrontal cortex, orbitofrontal cortex, rectus gyrus, and anterior cingulate cortex), the limbic striatum, and thalamus compared to controls. In the bvFTD patients, the involvement of the limbic CSTC circuit was associated with the severity of behavior disruption, as measured by the frontal behavior inventory, the disinhibition subscale, and the apathy subscale. Notably, asymptomatic MAPT carriers had weakened frontostriatal connectivity but enhanced striatothalamus and thalamofrontal connectivity within the limbic CSTC circuit compared with noncarriers.

Conclusion

These findings suggested that aberrant metabolic connectivity within the limbic CSTC circuit is present in symptomatic and even asymptomatic stages of bvFTD. Thus, metabolic connectivity patterns could be used as a potential biomarker to detect the presymptomatic stage and track disease progression.
Stability and biosafety of human epidermal stem cell for wound repair: preclinical evaluation
Authors: Zhao Xiaohong , Li Xue , Wang Ying , Guo Yicheng , Huang Yong , Lv Dalun , Lei Mingxing , Yu Shicang , Luo Gaoxing , Zhan Rixing
Published: January 2023

Background

Cell therapy is a key technology to prevent sacrificing normal skin. Although some studies have shown the promise of human epidermal stem cells (EpiSCs), the efficacy, biosafety and quality control of EpiSC therapy have not been systematically reported.

Methods

The biosafety, stemness maintenance and wound repair of EpiSC were systematically verified by in vitro and in vivo experiments. EpiSC were prepared from the foreskin using a collagen type IV rapid adherence method. The EpiSCs were identified by flow cytometry, immunofluorescence staining and cell morphology. The well-growing passage 1 (P1) EpiSCs were used to determine the proliferation curve (counting method). EpiSC clone formation assay was performed by Giemsa staining. Nude mice were used to prepare a full-thickness skin defect wound model to detect the repair effect of EpiSCs. The biosafety of EpiSCs was double tested in vitro and in vivo.

Results

The results showed that the expression of specific markers and clone formation efficiency was stable when passage 1 (P1) to P8 cells were cultured, and the stemness rate of P8 cells was close to 85.1%. EpiSCs were expanded in vitro for 25 days, the number of cells reached 2.5 × 108, and the transplantable area was approximately 75% of the total body surface area (TBSA). At 45 days, the total number of cells was approximately 30 billion, and the transplantable area was approximately the size of a volleyball court. A nude mouse wound model indicated that EpiSCs could rapidly close a wound. On postinjury day 7, the wound epithelialization rate in the cell transplantation group was significantly higher than that in the NaCl group (P < 0.05). In vitro, cell senescence increased, and telomerase activity decreased in P1 to P8 EpiSCs. In vivo, there were no solid tumors or metastatic tumors after EpiSC (P8) transplantation. In addition, the quality control of cultured cells met the clinical application criteria for cell therapy.

Conclusion

This preclinical study showed the stability and biosafety of human EpiSC therapy for wound repair.

Graphical Abstract
An analysis of stand-level size distributions of decay-affected Norway spruce trees based on harvester data
Authors: Räty Janne , Hietala Ari M. , Breidenbach Johannes , Astrup Rasmus
Published: January 2023

Key message

We studied size distributions of decay-affected Norway spruce trees using cut-to-length harvester data. The harvester data comprised tree-level decay and decay severity recordings from 101 final felling stands, which enabled to analyze relationships between size distributions of all and decay-affected trees. Distribution matching technique was used to transfer the size distribution of all trees into the diameter at breast height (DBH) distribution of decay-affected trees.

Context

Stem decay of Norway spruce (Picea abies [L.] Karst.) results in large economic losses in timber production in the northern hemisphere. Forest management planning typically requires information on tree size distributions. However, size distributions of decay-affected trees generally remain unknown impeding decision-making in forest management planning.

Aims

Our aim was to analyze and model relationships between size distributions of all and decay-affected Norway spruce trees at the level of forest stands.

Methods

Cut-to-length harvester data of 93,456 trees were collected from 101 final felling stands in Norway. For each Norway spruce tree (94% of trees), the presence and severity of stem decay (incipient and advanced) were recorded. The stand-level size distributions (diameter at breast height, DBH; height, H) of all and decay-affected trees were described using the Weibull distribution. We proposed distribution matching (DM) models that transform either the DBH or H distribution of all trees into DBH distributions of decay-affected trees. We compared the predictive performance of DMs with a null-model that refers to a global Weibull distribution estimated based on DBHs of all harvested decay-affected trees.

Results

The harvester data showed that an average-sized decay-affected tree is larger and taller compared with an average-sized tree in a forest stand, while trees with advanced decay were generally shorter and thinner compared with trees having incipient decay. DBH distributions of decay-affected trees can be matched with smaller error index (EI) values using DBH (EI = 0.14) than H distributions (EI = 0.31). DM clearly outperformed the null model that resulted in an EI of 0.32.

Conclusions

The harvester data analysis showed a relationship between size distributions of all and decay-affected trees that can be explained by the spread biology of decay fungi and modeled using the DM technique.
Intermediate data fault-tolerant method of cloud computing accounting service platform supporting cost-benefit analysis
Authors: Jin Taolan , Zhang Bo
Published: January 2023

This study mainly aims at the intermediate data fault-tolerant method of cloud computing accounting service platform supporting cost-benefit analysis, which aims at providing cost-benefit analysis function for the platform and strengthening the fault-tolerant ability of the intermediate data of the platform. The invention discloses a method for constructing an enterprise cloud computing accounting service platform. Collect the internal and external accounting service system data of an enterprise by using an accounting service platform network environment provided by a cloud service provider. Transmit the data to a data processing and storage layer data warehouse for storage after data cleaning, extraction and processing. Then, call the collected data through the data processing and storage layer to analyze the transaction cost-benefit of the enterprise. The intermediate data fault-tolerant model is constructed. After being solved by the ant colony algorithm, the intermediate data generated in the process of cost-benefit analysis and other accounting services are fault-tolerant processed. Finally, the platform accounting service results are output to the interactive interface through the data output display layer. The highest data availability probability of the method proposed in this study is 0. 98, which indicates that the method has high data availability after fault-tolerant processing, and can effectively realize the interaction with users. The experimental analysis shows that the method proposed in this study can effectively analyze the transaction costs and benefits of enterprises. The probability of data availability after fault-tolerant processing is higher, and a load of reading and writing is lower.
Healthcare-associated infections in Dutch hospitals during the COVID-19 pandemic
Authors: Verberk Janneke D. M. , van der Kooi Tjallie I. I. , Kampstra Nynke A. , Reimes Naomi , van Rooden Stephanie M. , Hopmans Titia E. M. , Geerlings Suzanne E. , de Greeff Sabine C.
Published: January 2023

Background

During the COVID-19 pandemic hospitals reorganized their resources and delivery of care, which may have affected the number of healthcare-associated infections (HAIs). We aimed to quantify changes in trends in the number of HAIs in Dutch hospitals during the COVID-19 pandemic.

Methods

National surveillance data from 2016 to 2020 on the prevalence of HAIs measured by point prevalence surveys, and the incidence of surgical site infections (SSIs) and catheter-related bloodstream infections (CRBSIs) were used to compare rates between the pre-pandemic (2016–February 2020) and pandemic (March 2020–December 2020) period.

Results

The total HAI prevalence among hospitalised patients was higher during the pandemic period (7.4%) compared to pre-pandemic period (6.4%), mainly because of an increase in ventilator-associated pneumonia (VAP), gastro-intestinal infections (GIs) and central nervous system (CNS) infections. No differences in SSI rates were observed during the pandemic, except for a decrease after colorectal surgeries (6.3% (95%-CI 6.0–6.6%) pre-pandemic versus 4.4% (95%-CI 3.9–5.0%) pandemic). The observed CRBSI incidence in the pandemic period (4.0/1,000 CVC days (95%-CI 3.2–4.9)) was significantly higher than predicted based on pre-pandemic trends (1.4/1000 (95%-CI 1.0–2.1)), and was increased in both COVID-19 patients and non-COVID-19 patients at the intensive care unit (ICU).

Conclusions

Rates of CRBSIs, VAPs, GIs and CNS infections among hospitalised patients increased during the first year of the pandemic. Higher CRBSI rates were observed in both COVID-19 and non-COVID-19 ICU population. The full scope and influencing factors of the pandemic on HAIs needs to be studied in further detail.
Antibiotic use by poultry farmers in Kiambu County, Kenya: exploring practices and drivers of potential overuse
Authors: Kariuki Jeniffer Waiyego , Jacobs Jan , Ngogang Marie Paule , Howland Olivia
Published: January 2023

Background

Antibiotic resistance is a global concern threatening achievements in health care since the discovery of antibiotics. In Kenya, this topic remains understudied in a context of rising demand for livestock products, intensification and the concomitant increase in antibiotic use. Our study investigates drivers and practices of antibiotic use in poultry farming. The study was conducted in Kiambu County, Kenya.

Methods

A qualitative research methodology was employed: fourteen key informant interviews, twenty in-depth interviews, and four focus group discussions were undertaken. The interviews were semi-structured. Themes and subthemes from the interviews were generated through inductive analysis.

Findings

Of the farmers interviewed, sixty eight percent were female, thirty three percent of the sampled farmers could not read, and the majority (eight five percent) of farmers had reared poultry for at least ten years. Research findings showed that farmers extensively used antibiotics. Antibiotic use was influenced by factors such as high disease burden, access to medicines and economic pressure. Common practices included prophylactic use, use of antibiotics to enhance production, self-prescription use, use of combination antibiotics (A combination antibiotic is one in which two or more antibiotics are added together for additional therapeutic effect.), and antibiotics classified as critically important in human medicine. Key information sources for the farmers were agro- veterinary dispensers, sellers of day-old chicks, and peer-learning. External factors driving the inappropriate use of antibiotics included access to the antibiotics, influence by marketers such as sellers of day-old chicks, and branding. Use of antibiotics was also driven by economic factors among the farmers, sellers of day-old chicks and agro-veterinary dispensers.

Conclusions

Our findings indicate widespread use of antibiotics among poultry farmers in our study site. The use of antibiotics is influenced by an interplay of issues at the farmers’ level as well as broader social, economic and structural level factors. A multifaceted One Health approach focusing on regulatory frameworks, knowledge transfer, and research is required to promote stewardship and judicious use of antibiotics.
A pseudo-outbreak of MRSA due to laboratory contamination related to MRSA carriage of a laboratory staff member
Authors: Houkes Karlijn M. G. , Stohr Joep J. J. M. , Gast Karin B. , Couderé Karen , Weterings Veronica , Mutsaers - van Oudheusden Anne , Buiting Anton G. M. , Verweij Jaco J.
Published: January 2023

Background

Methicillin resistant Staphylococcus aureus (MRSA) is a major burden for hospitals globally. However, in the Netherlands, the MRSA prevalence is relatively low due to the ‘search and destroy’ policy. Routine multiple-locus variable-number of tandem repeat analysis (MLVA) of MRSA isolates supports outbreak detection. However, whole genome multiple locus sequence typing (wgMLST) is superior to MLVA in identifying (pseudo-)outbreaks with MRSA. The present study describes a pseudo-outbreak of MRSA at the bacteriology laboratory of a large Dutch teaching hospital.

Methods

All staff members of the bacteriology laboratory of the Elisabeth-TweeSteden hospital were screened for MRSA carriage, after a laboratory contamination with MRSA was suspected. Clonal relatedness between the index isolate and the MRSA isolates from laboratory staff members and all previous MRSA isolates from the Elisabeth-TweeSteden hospital with the same MLVA-type as the index case was examined based on wgMLST using whole genome sequencing.

Results

One of the staff members was identified as the probable source of the laboratory contamination, because of carriage of a MRSA possessing the same MLVA-type as the index case. Eleven other isolates with the same molecular characteristics were found in the database, of which seven were retrospectively suspected of contamination. Clonal relatedness was found between ten isolates, including the isolate found in the staff member and the MRSA found in the index patient with a maximum of eleven alleles difference. All isolates were epidemiologically linked through the laboratory staff member, who had worked on all these cultures.

Conclusions

The present study describes a MRSA pseudo-outbreak over a 2.5-year period due to laboratory contamination caused by a MRSA carrying laboratory staff member involving nine patients. In case of unexpected bacteriological findings, the possibility of a laboratory contamination should be considered.