bluuebunny/crossref_metadata_2025 huggingface dataset:
Power outage mediates the associations between major storms and hospital admission of chronic obstructive pulmonary disease
Authors: Qu Yanji , Zhang Wangjian , Ye Bo , Penta Samantha , Dong Guanghui , Liu Xiaoqing , Lin Shao
Published: October 2021

Background

Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide with continuous rise. Limited studies indicate that COPD was associated with major storms and related power outages (PO). However, significant gaps remain in understanding what PO’s role is on the pathway of major storms-COPD. This study aimed to examine how PO mediates the major storms-COPD associations.

Methods

In this time-series study, we extracted all hospital admissions with COPD as the principal diagnosis in New York, 2001–2013. Using distributed lag nonlinear models, the hospitalization rate during major storms and PO was compared to non-major storms and non-PO periods to determine the risk ratios (RRs) for COPD at each of 0–6 lag days respectively after controlling for time-varying confounders and concentration of fine particulate matter (PM2.5). We then used Granger mediation analysis for time series to assess the mediation effect of PO on the major storms-COPD associations.

Results

The RRs of COPD hospitalization following major storms, which mainly included flooding, thunder, hurricane, snow, ice, and wind, were 1.23 to 1.49 across lag 0–6 days. The risk was strongest at lag3 and lasted significantly for 4 days. Compared with non-outage periods, the PO period was associated with 1.23 to 1.61 higher risk of COPD admissions across lag 0–6 days. The risk lasted significantly for 2 days and was strongest at lag2. Snow, hurricane and wind were the top three contributors of PO among the major storms. PO mediated as much as 49.6 to 65.0% of the major storms-COPD associations.

Conclusions

Both major storms and PO were associated with increased hospital admission of COPD. PO mediated almost half of the major storms-COPD hospitalization associations. Preparation of surrogate electric system before major storms is essential to reduce major storms-COPD hospitalization.
Laparoscopic splenectomy both for primary cytoreductive surgery for advanced ovarian cancer and for secondary surgery for isolated spleen recurrence: feasibility and technique
Authors: Macciò Antonio , Sanna Elisabetta , Lavra Fabrizio , Chiappe Giacomo , Petrillo Marco , Madeddu Clelia
Published: October 2021

Background

This study investigated the feasibility and safety of laparoscopic splenectomy conducted in the contexts of both laparoscopic secondary surgery for isolated recurrence in the spleen and primary laparoscopic cytoreductive surgery for advanced ovarian cancer.

Methods

We performed a perspective observational study including all consecutive patients with ovarian cancer who underwent laparoscopic splenectomy as part of primary cytoreductive procedures for advanced stage ovarian cancer or secondary surgery for isolated splenic recurrence between January 2016 and May 2020.

Results

We enrolled 13 consecutive patients, candidate to laparoscopic splenectomy as part of primary cytoreductive procedures for advanced stage ovarian cancer (6 patients) or secondary surgery for isolated splenic recurrence of platinum-sensitive ovarian cancer (7 patients). Median operative time (509 min [range, 200–845]) for primary cytoreductive surgery varied according to surgical complexity depending on the extensiveness of the disease. Median operative time for secondary surgery for isolated splenic metastasis was 253 min (90–380). Only 1 patient with isolated splenic recurrence required conversion to an open approach. No intraoperative complication occurred, and no intraoperative blood transfusions were required. Median hospital stay was 3 days (range, 2–5) for isolated recurrence and 9 days (7–18) for primary cytoreductive surgery. Complete tumor resection was achieved in all patients. Median time from surgery to adjuvant chemotherapy was 16 days (7–24). All six patients who underwent laparoscopic splenectomy during primary cytoreductive surgery remain alive, four of whom exhibit no evidence of disease (median follow-up 25 months [4–36]). Among patients who underwent laparoscopic splenectomy during secondary surgery for isolated splenic relapse, all patients are alive and only one had a central diaphragmatic relapse 2 years after surgery (median follow-up 17 months ([5–48 months]).

Conclusions

The laparoscopic approach to splenectomy is feasible and safe both in patients undergoing primary cytoreductive surgery for advanced stage disease and those with isolated recurrence of ovarian cancer, without compromising survival and allowing early initiation of postoperative systemic chemotherapy.
Next of kin’s experiences of registered nurses’ leadership close to older adults in municipal home care in Sweden: an interview study
Authors: Claesson Maria , Jonasson Lise-Lotte , Josefsson Karin
Published: October 2021

Background

Next of kin to older adults over 65 years in municipal home care are concerned whether their older adults’ needs are being met. In municipal home care, the registered nurses’ leadership is important and complex, entailing multi-artist skills involving the older adults and their next of kin. Yet, little is known about next of kin’s experiences of registered nurses’ leadership. Thus, the aim of this study was to explore next of kin’s experiences of registered nurses’ leadership close to older adults in municipal home care.

Methods

Individual telephone interviews were conducted with next of kin (n = 11) of older adults from April to September 2020 in two municipalities in western Sweden. Data were analysed using qualitative content analysis.

Results

The results are presented with the theme, registered nurses do what they can, including two categories, interaction and competence, and the subcategories, relationship, communication, availability, responsibility, team leadership and cooperation. Registered nurses’ leadership was experienced as a balancing act between their commitments and what they were able to achieve.

Conclusions

Next of kin’s experiences of registered nurses’ leadership can contribute knowledge that will strengthen and prepare registered nurses for their leadership roles. This knowledge can support the development of policies for organisational preconditions that ensure quality and safe care to older adults in municipal home care.
Cost-utility of two minimally-invasive surgical techniques for operable oropharyngeal cancer: transoral robotic surgery versus transoral laser microsurgery
Authors: Parimbelli Enea , Soldati Federico , Duchoud Lorry , Armas Gian Luca , de Almeida John , Broglie Martina , Quaglini Silvana , Simon Christian
Published: October 2021

Background

In the past few decades, a re-evaluation of treatment paradigms of head and neck cancers with a desire to spare patients the treatment-related toxicities of open surgery, has led to the development of new minimally invasive surgical techniques to improve outcomes. Besides Transoral Laser Microsurgery (TLM), a newroboticsurgical technique namely Transoral Robotic Surgery (TORS) emerged for the first time as one of the two most prominent and widely used minimally invasive surgical approaches particularly for the treatment of oropharyngeal cancer, a sub-entity of head and neck cancers. Recent population-level data suggest equivalent tumor control, but different total costs, and need for adjuvant chemoradiation. A comparative analysis of these two techniques is therefore warranted from the cost-utility (C/U) point of view.

Methods

A cost-utility analysis for comparing TORS and TLM was performed using a decision-analytical model. The analyses adopted the perspective of a Swiss hospital. Two tertiary referral centers in Lausanne and Zurich provided data for model quantificantion.

Results

In the base case analysis TLM dominates TORS. This advantage remains robust, even if the costs for TORS reduce by up to 25%. TORS begins to dominate TLM, if less than 59,7% patients require adjuvant treatment, whereby in an interval between 55 and 62% cost effectiveness of TORS is sensitive to the prescription of adjuvant chemoradiation therapy (CRT). Exceeding 29% of TLM patients requiring a revision of surgical margins renders TORS more cost-effective.

Conclusion

Non-robotic endoscopic surgery (TLM) is more cost-effective than robotic endoscopic surgery (TORS) for the treatment of oropharyngeal cancers. However, this advantage is sensitive to various parameters, i.e.to the number of re-operations and adjuvant treatment.
Changes in home care clients’ characteristics and home care in five European countries from 2001 to 2014: comparison based on InterRAI - Home Care data
Authors: Kristinsdottir I. V. , Jonsson P. V. , Hjaltadottir I. , Bjornsdottir K.
Published: October 2021

Background

Policymakers advocate extended residence in private homes as people age, rather than relocation to long-term care facilities. Consequently, it is expected that older people living in their own homes will be frailer and have more complex health problems over time. Therefore, community care for aging people is becoming increasingly important to facilitate prevention of decline in physical and cognitive abilities and unnecessary hospital admission and transfer to a nursing home. The aim of this study was to examine changes in the characteristic of home care clients and home care provided in five European countries between 2001 and 2014 and to explore whether home care clients who are most in need of care receive the care required.

Methods

This descriptive study used data from two European research projects, Aged in Home Care (AdHOC; 2001–2002) and Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of Community Care (IBenC; 2014–2016). In both projects, the InterRAI-Home Care assessment tool was used to assess a random sample of home care clients 65 years and older in five European countries. These data facilitate a comparison of physical and cognitive health and the provided home care between countries and study periods.

Results

In most participating countries, both cognitive (measured on the Cognitive Performance Scale) and functional ability (measured on the Activities of Daily Living Hierarchy scale) of home care clients deteriorated over a 10-year period. Home care provided increased between the studies. Home care clients who scored high on the physical and cognitive scales also received home care for a significantly higher duration than those who scored low.

Conclusion

Older people in several European countries remain living in their own homes despite deteriorating physical and cognitive skills. Home care services to this group have increased. This indicates that the government policy of long-term residence at own home among older people, even in increased frailty, has been realised.
Identifying carbohydrate-active enzymes of Cutaneotrichosporon oleaginosus using systems biology
Authors: Fuchs Tobias , Melcher Felix , Rerop Zora Selina , Lorenzen Jan , Shaigani Pariya , Awad Dania , Haack Martina , Prem Sophia Alice , Masri Mahmoud , Mehlmer Norbert , Brueck Thomas B.
Published: October 2021

Background

The oleaginous yeast Cutaneotrichosporon oleaginosus represents one of the most promising microbial platforms for resource-efficient and scalable lipid production, with the capacity to accept a wide range of carbohydrates encapsulated in complex biomass waste or lignocellulosic hydrolysates. Currently, data related to molecular aspects of the metabolic utilisation of oligomeric carbohydrates are sparse. In addition, comprehensive proteomic information for C. oleaginosus focusing on carbohydrate metabolism is not available.

Results

In this study, we conducted a systematic analysis of carbohydrate intake and utilisation by C. oleaginosus and investigated the influence of different di- and trisaccharide as carbon sources. Changes in the cellular growth and morphology could be observed, depending on the selected carbon source. The greatest changes in morphology were observed in media containing trehalose. A comprehensive proteomic analysis of secreted, cell wall-associated, and cytoplasmatic proteins was performed, which highlighted differences in the composition and quantity of secreted proteins, when grown on different disaccharides. Based on the proteomic data, we performed a relative quantitative analysis of the identified proteins (using glucose as the reference carbon source) and observed carbohydrate-specific protein distributions. When using cellobiose or lactose as the carbon source, we detected three- and five-fold higher diversity in terms of the respective hydrolases released. Furthermore, the analysis of the secreted enzymes enabled identification of the motif with the consensus sequence LALL[LA]L[LA][LA]AAAAAAA as a potential signal peptide.

Conclusions

Relative quantification of spectral intensities from crude proteomic datasets enabled the identification of new enzymes and provided new insights into protein secretion, as well as the molecular mechanisms of carbo-hydrolases involved in the cleavage of the selected carbon oligomers. These insights can help unlock new substrate sources for C. oleaginosus, such as low-cost by-products containing difficult to utilize carbohydrates. In addition, information regarding the carbo-hydrolytic potential of C. oleaginosus facilitates a more precise engineering approach when using targeted genetic approaches. This information could be used to find new and more cost-effective carbon sources for microbial lipid production by the oleaginous yeast C. oleaginosus.
Whole-cell catalysis by surface display of fluorinase on Escherichia coli using N-terminal domain of ice nucleation protein
Authors: Feng Xinming , Jin Miaomiao , Huang Wei , Liu Wei , Xian Mo
Published: October 2021

Background

Fluorinases play a unique role in the production of fluorine-containing organic molecules by biological methods. Whole-cell catalysis is a better choice in the large-scale fermentation processes, and over 60% of industrial biocatalysis uses this method. However, the in vivo catalytic efficiency of fluorinases is stuck with the mass transfer of the substrates.

Results

A gene sequence encoding a protein with fluorinase function was fused to the N-terminal of ice nucleation protein, and the fused fluorinase was expressed in Escherichia coli BL21(DE3) cells. SDS-PAGE and immunofluorescence microscopy were used to demonstrate the surface localization of the fusion protein. The fluorinase displayed on the surface showed good stability while retaining the catalytic activity. The engineered E.coli with surface-displayed fluorinase could be cultured to obtain a larger cell density, which was beneficial for industrial application. And 55% yield of 5′-fluorodeoxyadenosine (5′-FDA) from S-adenosyl-L-methionine (SAM) was achieved by using the whole-cell catalyst.

Conclusions

Here, we created the fluorinase-containing surface display system on E.coli cells for the first time. The fluorinase was successfully displayed on the surface of E.coli and maintained its catalytic activity. The surface display provides a new solution for the industrial application of biological fluorination.

Graphical Abstract
Carboxypeptidase N1 is anticipated to be a synergy metrics for chemotherapy effectiveness and prognostic significance in invasive breast cancer
Authors: Cui Ranliang , Wang Chaomin , Li Tiantian , Hua Jialei , Zhao Ting , Ren Li , Wang Yichao , Li Yueguo
Published: October 2021

Background

The incidence and mortality of invasive breast cancer (IBC) are increasing annually. Hence, it is urgently needed to determine reliable biomarkers for not only monitoring curative effects, but evaluating prognosis. In present study, we aim to determine the potential role of Carboxypeptidase N1 (CPN1) in IBC tissues on chemotherapeutic efficacy and poor prognosis.

Methods

The expression level of CPN1 in IBC tissue samples (n = 123) was quantified by tissue microarray technique and immunohistochemical staining. Moreover, sera of IBC patients (n = 34) that underwent three to five consecutive chemotherapy sessions were collected. The patients were randomly stratified into a training (n = 15) as well as a validation group (n = 19). The expression of serum CA153 and CPN1 was quantified by electrochemiluminescence and ELISA assay, respectively.

Results

By univariate and multivariate Cox regression analysis, we show that CPN1 expression in IBC tissues, as an independent risk factor, is related to a poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). Analysis of the data revealed that CPN1 over-expression could be consistently linked to adverse clinicopathological features such as lymph node metastasis and the pathological stage (pTNM) (P < 0.05). The serum CPN1 level trajectory of individual patients generally decreased during chemotherapy. In line with these findings were changes in the follow-up ultrasonography and a consistent decrease in serum CPN1 levels. The comparison of the area under the receiver operating curves (ROC) revealed that CPN1 has a better surveillance value than CA153 in the training (AUCCPN1 = 0.834 vs. AUCCA153 = 0.724) as well as the validation set (AUCCPN1 = 0.860 vs. AUCCA153 = 0.720) when comparing cycle2 versus cycle3.

Conclusions

CPN1 is a suitable potential biomarker for chemotherapeutic surveillance purposes as well as being an appropriate prognostic indicator which would support an improved chemotherapy regimen.
Proteo-transcriptomics meta-analysis identifies SUMO2 as a promising target in glioblastoma multiforme therapeutics
Authors: Krishna Aswani P. , John Sebastian , Shinde Puja Laxmanrao , Mishra Rashmi
Published: October 2021

Background

Glioblastoma multiforme (GBM) is a deadly brain tumour with minimal survival rates due to the ever-expanding heterogeneity, chemo and radioresistance. Kinases are known to crucially drive GBM pathology; however, a rationale therapeutic combination that can simultaneously inhibit multiple kinases has not yet emerged successfully.

Results

Here, we analyzed the GBM patient data from several publicly available repositories and deduced hub GBM kinases, most of which were identified to be SUMOylated by SUMO2/3 isoforms. Not only the hub kinases but a significant proportion of GBM upregulated genes involved in proliferation, metastasis, invasion, epithelial-mesenchymal transition, stemness, DNA repair, stromal and macrophages maintenance were also identified to be the targets of SUMO2 isoform. Correlatively, high expression of SUMO2 isoform was found to be significantly associated with poor patient survival.

Conclusions

Although many natural products and drugs are evidenced to target general SUMOylation, however, our meta-analysis strongly calls for the need to design SUMO2/3 or even better SUMO2 specific inhibitors and also explore the SUMO2 transcription inhibitors for universally potential, physiologically non-toxic anti-GBM drug therapy.

Graphical Abstract
Effect of roof colour on indoor temperature and human comfort levels, with implications for malaria control: a pilot study using experimental houses in rural Gambia
Authors: Carrasco-Tenezaca Majo , Jatta Ebrima , Jawara Musa , Bradley John , Pinder Margaret , D’Alessandro Umberto , Knudsen Jakob , Lindsay Steve W.
Published: October 2021

Background

In rural sub-Saharan Africa, thatch roofs are being replaced by metal roofs. Metal roofing, however, increases indoor temperatures above human comfort levels, and thus makes it more likely that residents will not use an insecticide-treated bed net (ITN) at night. Whether the colour of a metal roof affects indoor temperature and human comfort was assessed.

Methods

Two identical, experimental houses were constructed with metal roofs in rural Gambia. Roof types were: (1) original bare-metal, (2) painted with red oxide primer or (3) white gloss, to reflect solar radiation. Pairwise comparisons were run in six, five-night blocks during the malaria season 2018. Indoor climate was measured in each house and multivariate analysis used to compare indoor temperatures during the day and night.

Results

From 21.00 to 23.59 h, when most residents decide whether to use an ITN or not, the indoor temperature of a house with a bare metal roof was 31.5 °C (95% CI  31.2–31.8 °C), a red roof, 30.3 °C (95% CI 30.0–30.6) and a white roof, 29.8 °C (95% CI 29.4–30.1). During the same period, red-roofed houses were 1.23 °C cooler (95% CI 1.22–1.23) and white roofs 1.74 °C cooler (95% CI 1.70–1.79) than bare-metal roofed houses (p  < 0.001). Similar results were found from 00.00 to 06.00 h. Maximum daily temperatures were 0.93 °C lower in a white-roofed house (95% CI  0.10–0.30, p  < 0.001), but not a red roof (mean maximum temperature difference  = 0.44 °C warmer, 95% CI  0.43–0.45, p  = 0.081), compared with the bare-metal roofed houses. Human comfort analysis showed that from 21.00 to 23.59 h houses with white roofs (comfortable for 87% time) were more comfortable than bare-metal roofed houses (comfortable for 13% time; odds ratio  = 43.7, 95% CI 27.5–69.5, p  < 0.001). The cost of painting a metal roof white is approximately 31–68 USD.

Conclusions

Houses with a white roof were consistently cooler and more comfortable than those with a bare metal roof. Painting the roofs of houses white is a cheap way of making a dwelling more comfortable for the occupants and could potentially increase bed net use in hot humid countries.
Prevalence of asymptomatic malaria, submicroscopic parasitaemia and anaemia in Korogwe District, north-eastern Tanzania
Authors: Hayuma Paul M. , Wang Christian W. , Liheluka Edwin , Baraka Vito , Madebe Rashid A. , Minja Daniel T. R. , Misinzo Gerald , Alifrangis Michael , Lusingu John P. A.
Published: October 2021

Background

Asymptomatic malaria infections largely remain undetected and act as a reservoir for continuous transmission. The study assessed the prevalence of submicroscopic asymptomatic malaria infections and anaemia in two rural low (300 m above sea level) and highland (700 m asl) settings of Korogwe District north-eastern Tanzania.

Methods

A cross-sectional malariometric survey involving individuals aged 0–19 years was conducted in June 2018 in the two rural villages. Venous blood was collected from eligible study participants for estimation of haemoglobin level, detection of malaria by rapid diagnostic test (RDT), quantification of malaria parasitaemia by microscopy, as well as dried blood spot (DBS) for determining submicroscopic infections by PCR targeting the small subunit of the ribosomal ribonucleic acid (ssrRNA) of human Plasmodium.

Results

Out of 565 individuals tested, 211 (37.3%) were malaria positive based on RDT, whereas only 81 (14.3%) were positive by microscopy. There was no significant difference in the prevalence between the highland and the lowland village, p = 0.19 and p = 0.78 microscopy and RDT, respectively. Three out of 206 (1.5%) RDT/microscopy negative samples were P. falciparum positive by PCR. Of the 211 RDT and 81 microscopy positive, 130 (61.6%) and 33 (40.7%), respectively, were defined as being asymptomatic. Of the 565 individuals, 135 (23.9%) were anaemic (haemoglobin < 11 g/dL) out of which 5.2% were severely anaemic. The risk of being anaemic was significantly higher among individuals with asymptomatic malaria as compared to those without malaria as confirmed by RDT (AOR = 2.06 (95% CI 1.32–3.20) while based on microscopic results there was no significant differences observed (AOR = 2.09, 95% CI 0.98–4.47). Age and altitude had no effect on the risk of anaemia even after adjusting for asymptomatic malaria.

Conclusions

Asymptomatic malaria is associated with an increased risk of having anaemia in the study communities. The findings highlight the need for targeted interventions focusing on asymptomatic infections which is an important risks factor for anaemia in the community and act as a source of continued transmission of malaria in the study area.
Changes in dairy product consumption and subsequent type 2 diabetes among individuals with prediabetes: Tehran Lipid and Glucose Study
Authors: Yuzbashian Emad , Asghari Golaleh , Mirmiran Parvin , Chan Catherine B. , Azizi Fereidoun
Published: October 2021

Background

People with prediabetes can postpone or even reverse progression to type 2 diabetes (T2D) by making dietary changes. This study aimed to examine the association of changes in consumption of total and specific types of dairy products with the subsequent risk of incident T2D among individuals with prediabetes.

Method

This cohort study included 639 individuals (50% female, mean age 47.3 years) of the Tehran Lipid and Glucose Study (TLGS) who had prediabetes at baseline. We assessed 3-year changes in the consumption of dairy products using a food frequency questionnaire. Using multivariable logistic regression, odds ratios (OR) and 95% confidence intervals (CI) were calculated for the association of changes in intake of total and subtypes of dairy products during a 3-year interval with the risk of incident T2D in the subsequent 3 years.

Results

After almost 9 years of follow-up, the incidence of T2D was 25.2%. Compared with individuals whose intake remained relatively stable over 3 years, those who decreased consumption of total dairy (> 0.5 servings/day) had a higher T2D risk (OR = 1.56; 95% CI: 1.02 to 2.41). Increasing low-fat dairy consumption by 0.50 serving/d was associated with a lower risk of T2D (OR = 0.56; 95% CI: 0.35 to 0.90) compared with stable consumption. Those who increased consumption of low-fat milk (OR = 0.59; 95% CI: 0.37 to 0.92) and low-fat yogurt (OR = 0.55; 95% CI: 0.33 to 0.93) had a lower risk of T2D than those who were relatively stable in their consumption. Replacing low-fat milk and yogurt with regular cheese was associated with 66 and 47% higher risk of T2D, respectively.

Conclusion

In individuals with prediabetes, increasing consumption of low-fat dairy, low-fat milk, and low-fat yogurt had reduced risk of subsequent T2D. These data suggest a role of low-fat dairy products in the prevention of T2D among prediabetes patients.
Domestic use of pesticides during early periods of development and risk of testicular germ cell tumors in adulthood: a French nationwide case-control study
Authors: Danjou Aurélie M. N. , Pérol Olivia , Coste Astrid , Faure Elodie , Béranger Rémi , Boyle Helen , Belladame Elodie , Grassot Lény , Dubuis Matthieu , Spinosi Johan , Bouaoun Liacine , Fléchon Aude , Bujan Louis , Drouineaud Véronique , Eustache Florence , Berthaut Isabelle , Perrin Jeanne , Brugnon Florence , Charbotel Barbara , Schüz Joachim , Fervers Béatrice ,   For the TESTIS study group
Published: October 2021

Background

Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development.

Methods

We conducted a case-control study of 304 TGCT cases, aged 18–45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants’ mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son’s birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression.

Results

Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80–2.01) or herbicides (OR = 1.15, CI = 0.67–2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04–2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26–4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06–5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12–3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype.

Conclusions

Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.
CXCR5 down-regulation alleviates cognitive dysfunction in a mouse model of sepsis-associated encephalopathy: potential role of microglial autophagy and the p38MAPK/NF-κB/STAT3 signaling pathway
Authors: Shen Yanan , Zhang Yuan , Du Jiayue , Jiang Baochun , Shan Tao , Li Haojia , Bao Hongguang , Si Yanna
Published: October 2021

Background

Cognitive deficits are common in patients with sepsis. Previous studies in sepsis-associated encephalopathy (SAE) implicated the C-X-C chemokine receptor type (CXCR) 5. The present study used a mouse model of SAE to examine whether CXCR5 down-regulation could attenuate cognitive deficits.

Methods

Sepsis was induced in adult male C57BL/6 J and CXCR5−/− mice by cecal ligation and puncture (CLP). At 14–18 days after surgery, animals were tested in a Morris water maze, followed by a fear conditioning test. Transmission electron microscopy of hippocampal sections was used to assess levels of autophagy. Primary microglial cultures challenged with lipopolysaccharide (LPS) were used to examine the effects of short interfering RNA targeting CXCR5, and to investigate the possible involvement of the p38MAPK/NF-κB/STAT3 signaling pathway.

Results

CLP impaired learning and memory and up-regulated CXCR5 in hippocampal microglia. CLP activated hippocampal autophagy, as reflected by increases in numbers of autophagic vacuoles, conversion of microtubule-associated protein 1 light chain 3 (LC3) from form I to form II, accumulation of beclin-1 and autophagy-related gene-5, and a decrease in p62 expression. CLP also shifted microglial polarization to the M1 phenotype, and increased levels of IL-1β, IL-6 and phosphorylated p38MAPK. CXCR5 knockout further enhanced autophagy but partially reversed all the other CLP-induced effects, including cognitive deficits. Similar effects on autophagy and cytokine expression were observed after knocking down CXCR5 in LPS-challenged primary microglial cultures; this knockdown also partially reversed LPS-induced up-regulation of phosphorylated NF-κB and STAT3. The p38MAPK agonist P79350 partially reversed the effects of CXCR5 knockdown in microglial cultures.

Conclusions

CXCR5 may act via p38MAPK/NF-κB/STAT3 signaling to inhibit hippocampal autophagy during sepsis and thereby contribute to cognitive dysfunction. Down-regulating CXCR5 can restore autophagy and mitigate the proinflammatory microenvironment in the hippocampus.
Altered substrate metabolism in neurodegenerative disease: new insights from metabolic imaging
Authors: Cleland Nicholas R. W. , Al-Juboori Saif I. , Dobrinskikh Evgenia , Bruce Kimberley D.
Published: October 2021

Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and multiple sclerosis (MS), are relatively common and devastating neurological disorders. For example, there are 6 million individuals living with AD in the United States, a number that is projected to grow to 14 million by the year 2030. Importantly, AD, PD and MS are all characterized by the lack of a true disease-modifying therapy that is able to reverse or halt disease progression. In addition, the existing standard of care for most NDs only addresses the symptoms of the disease. Therefore, alternative strategies that target mechanisms underlying the neuropathogenesis of disease are much needed. Recent studies have indicated that metabolic alterations in neurons and glia are commonly observed in AD, PD and MS and lead to changes in cell function that can either precede or protect against disease onset and progression. Specifically, single-cell RNAseq studies have shown that AD progression is tightly linked to the metabolic phenotype of microglia, the key immune effector cells of the brain. However, these analyses involve removing cells from their native environment and performing measurements in vitro, influencing metabolic status. Therefore, technical approaches that can accurately assess cell-specific metabolism in situ have the potential to be transformative to our understanding of the mechanisms driving AD. Here, we review our current understanding of metabolism in both neurons and glia during homeostasis and disease. We also evaluate recent advances in metabolic imaging, and discuss how emerging modalities, such as fluorescence lifetime imaging microscopy (FLIM) have the potential to determine how metabolic perturbations may drive the progression of NDs. Finally, we propose that the temporal, regional, and cell-specific characterization of brain metabolism afforded by FLIM will be a critical first step in the rational design of metabolism-focused interventions that delay or even prevent NDs.
Integration of SARS-CoV-2 RNA in infected human cells by retrotransposons: an unlikely hypothesis and old viral relationships
Authors: Grandi Nicole , Tramontano Enzo , Berkhout Ben
Published: October 2021

Zhang et al. (Proc Natl Acad Sci 118:e2105968118, 2021) recently reported that SARS-CoV-2 RNA can be retrotranscribed and integrated into the DNA of human cells by the L1 retrotransposon machinery. This phenomenon could cause persistence of viral sequences in patients and may explain the prolonged PCR-positivity of SARS-CoV-2 infected patients, even long after the phase of active virus replication has ended. This commentary does critically review the available data on this topic and discusses them in the context of findings made for other exogenous viruses and ancestral endogenous retroviral elements.
Pathogen change of avian influenza virus in the live poultry market before and after vaccination of poultry in southern China
Authors: Guo Jin , Song Wentao , Ni Xiansheng , Liu Wei , Wu Jingwen , Xia Wen , Zhou Xianfeng , Wang Wei , He Fenglan , Wang Xi , Fan Guoyin , Zhou Kun , Chen Haiying , Chen Shengen
Published: October 2021

Background

The fifth wave of H7N9 avian influenza virus caused a large number of human infections and a large number of poultry deaths in China. Since September 2017, mainland China has begun to vaccinate poultry with H5 + H7 avian influenza vaccine. We investigated the avian influenza virus infections in different types of live poultry markets and samples before and after genotype H5 + H7 vaccination in Nanchang, and analyzed the changes of the HA subtypes of AIVs.

Methods

From 2016 to 2019, we monitored different live poultry markets and collected specimens, using real-time reverse transcription polymerase chain reaction (RT-PCR) technology to detect the nucleic acid of type A avian influenza virus in the samples. The H5, H7 and H9 subtypes of influenza viruses were further classified for the positive results. The χ2 test was used to compare the differences in the separation rates of different avian influenza subtypes.

Results

We analyzed 5,196 samples collected before and after vaccination and found that the infection rate of AIV in wholesale market (21.73%) was lower than that in retail market (24.74%) (P < 0.05). Among all the samples, the positive rate of sewage samples (33.90%) was the highest (P < 0.001). After vaccination, the positive rate of H5 and H7 subtypes decreased, and the positive rate of H9 subtype and untypable HA type increased significantly (P < 0.001). The positive rates of H9 subtype in different types of LPMs and different types of samples increased significantly (P < 0.01), and the positive rates of untypable HA type increased significantly in all environmental samples (P < 0.05).

Conclusions

Since vaccination, the positive rates of H5 and H7 subtypes have decreased, but the positive rates of H9 subtypes have increased to varying degrees in different testing locations and all samples. This results show that the government should establish more complete measures to achieve long-term control of the avian influenza virus.
Thirty-eight-year follow-up of the first patient of mandibular reconstruction with free vascularized fibula flap
Authors: Puricelli Edela , Chem Roberto Correa
Published: October 2021

Background

The mandible is responsible for vital functions of the stomatognathic system, and its loss results in functional and aesthetic impairment. Mandibular reconstruction with free fibula flap is considered the gold standard for mandibular reconstruction.

Case presentation

We describe here the 38-year follow-up of the patient who was the first case of mandibular reconstruction with free fibula flap reported in the literature. The original report describes a 27-year-old woman who had undergone extensive mandibulectomy due to an osteosarcoma. A microvascularized fibula flap was used for mandibular reconstruction in 1983. Two years later, a vestibulo-lingual sulcoplasty with skin graft was performed to allow the construction of a total dental prosthesis. Fifteen years after the initial treatment, an autologous iliac crest graft was placed in the fibula flap, aimed at increasing bone thickness and height for rehabilitation with implant supported prosthesis. In 2015, a rib graft was positioned in the mental region, enhancing the support to the soft tissues of the face and improving the oral function. A recent review of the patient shows well-balanced facial morphology and optimal functional results of the procedure.

Conclusions

The fibula flap method, described in 1975 and first reported for mandibular reconstruction in 1985, continues to be applied as originally described, especially where soft tissue damage is not extensive. Its use in reconstructive surgery was expanded by advancements in surgery and techniques such as virtual surgical planning. However, there is still a lack of evidence related to the long-term evaluation of outcomes. The present work represents the longest-term follow-up of a patient undergoing mandibular reconstruction with free vascularized fibula flap, presenting results showing that, even after 38 years, the procedure continues to provide excellent results.
A systematic study of independently-tuned room-specific PBS beam model in a beam-matched multiroom proton therapy system
Authors: Huang Yu-Hua , Fang Chunfeng , Yang Tao , Cao Lin , Zhang Gaolong , Qu Baolin , Zhang Yihang , Wang Zishen , Xu Shouping
Published: October 2021

Background

In the existing application of beam-matched multiroom proton therapy system, the model based on the commissioning data from the leading treatment room was used as the shared model. The purpose of this study is to investigate the ability of independently-tuned room-specific beam models of beam-matched gantries to reproduce the agreement between gantries’ performance when considering the errors introduced by the modeling process.

Methods

Raw measurements of two gantries’ dosimetric characteristics were quantitatively compared to ensure their agreement after initially beam-matched. Two gantries’ beam model parameters, as well as the model-based computed dosimetric characteristics, were analyzed to study the introduced errors and gantries’ post-modeling consistency. We forced two gantries to share the same beam model. The model-sharing patient-specific quality assurance (QA) tasks were retrospectively performed with 36 cancer patients to study the clinical impact of beam model discrepancies.

Results

Intra-gantry comparisons demonstrate that the modeling process introduced the errors to a certain extent indeed, which made the model-based reproduced results deviate from the raw measurements. Among them, the deviation introduced to the IDD curves was generally larger than that to the beam spots during modeling. Cross-gantry comparisons show that, from the beam model perspective, the introduced deviations deteriorated the high agreement of the dosimetric characteristics originally shown between two beam-matched gantries, but the cross-gantry discrepancy was still within the clinically acceptable tolerance. In model-sharing patient-specific QA, for the particular gantry, the beam model usage for intensity-modulated proton therapy (IMPT) QA plan generation had no significant effect on the actual delivering performance. All reached a high level of 95.0% passing rate with a 3 mm/3% criterion.

Conclusions

It was preliminary recognized that among beam-matched gantries, the independently-tuned room-specific beam model from any gantry is reasonable to be chosen as the shared beam model without affecting the treatment efficacy.
Degradation-driven changes in fine root carbon stocks, productivity, mortality, and decomposition rates in a palm swamp peat forest of the Peruvian Amazon
Authors: Dezzeo Nelda , Grandez-Rios Julio , Martius Christopher , Hergoualc’h Kristell
Published: October 2021

Background

Amazon palm swamp peatlands are major carbon (C) sinks and reservoirs. In Peru, this ecosystem is widely threatened owing to the recurrent practice of cuttingMauritia flexuosapalms for fruit harvesting. Such degradation could significantly damage peat deposits by altering C fluxes through fine root productivity, mortality, and decomposition rates which contribute to and regulate peat accumulation. Along a same peat formation, we studied an undegraded site (Intact), a moderately degraded site (mDeg) and a heavily degraded site (hDeg) over 11 months. Fine root C stocks and fluxes were monthly sampled by sequential coring. Concomitantly, fine root decomposition was investigated using litter bags. In the experimental design, fine root stocks and dynamics were assessed separately according to vegetation type (M. flexuosapalm and other tree species) andM. flexuosaage class. Furthermore, results obtained from individual palms and trees were site-scaled by using forest composition and structure.

Results

At the scale of individuals, fine root C biomass inM. flexuosaadults was higher at the mDeg site than at the Intact and hDeg sites, while in trees it was lowest at the hDeg site. Site-scale fine root biomass (Mg C ha−1) was higher at the mDeg site (0.58 ± 0.05) than at the Intact (0.48 ± 0.05) and hDeg sites (0.32 ± 0.03). Site-scale annual fine root mortality rate was not significantly different between sites (3.4 ± 1.3, 2.0 ± 0.8, 1.5 ± 0.7 Mg C ha−1 yr−1at the Intact, mDeg, and hDeg sites) while productivity (same unit) was lower at the hDeg site (1.5 ± 0.8) than at the Intact site (3.7 ± 1.2), the mDeg site being intermediate (2.3 ± 0.9). Decomposition was slow with 63.5−74.4% of mass remaining after 300 days and it was similar among sites and vegetation types.

Conclusions

The significant lower fine root C stock and annual productivity rate at the hDeg site than at the Intact site suggests a potential for strong degradation to disrupt peat accretion. These results stress the need for a sustainable management of these forests to maintain their C sink function.
Determinants of low birth weight deliveries at five referral hospitals in Western Area Urban district, Sierra Leone
Authors: Kargbo David Kabba , Nyarko Kofi , Sackey Samuel , Addo-Lartey Adolphina , Kenu Ernest , Anto Francis
Published: October 2021

Background

Low birth weight (LBW) contributes significantly to infant and child mortality. Each year, about 20 1million deliveries are LBW with 96.5% occurring in developing countries. Whiles the incidence of LBW is reducing in other districts of Sierra Leone, it has been reported to be increasing in the Western Area Urban district. Determining the risk factors in a specific geographic area is important for identifying mothers at risk and thereby for planning and taking appropriate action. The current study sought to identify factors associated with LBW deliveries in the Western Area Urban district of Sierra Leone.

Methods

A hospital-based unmatched 1:2 case-control study was conducted among mothers who delivered live singleton babies from November, 2019 to February, 2020 in five referral health facilities. Mothers were conveniently sampled and sequentially enrolled into the study after delivery. Their antenatal care cards were reviewed and a pre-tested questionnaire administered to the mothers. Data analysis was done using Stata 15.0 and association between maternal socio-demographic, socio-economic, obstetric and lifestyle factors and LBW assessed using bivariable and multivariable logistic regression analyses.

Results

A total of 438 mothers (146 cases and 292 controls), mean age: 24.2 (±5.8) and 26.1 (±5.5) years for cases and controls respectively participated in the study. Multivariable analysis revealed that being unemployed (AoR = 2.52, 95% CI 1.16–5.49, p = 0.020), having anaemia during pregnancy (AoR = 3.88, 95% CI 1.90–7.90, p <  0.001), having less than 2 years inter-pregnancy interval (AoR = 2.53, 95% CI 1.11–5.73, p = 0.026), and smoking cigarettes during pregnancy (AoR = 4.36, 95% CI 1.94–9.80, p <  0.001) were significantly associated with having LBW babies.

Conclusion

Factors associated with LBW identified were unemployment, anaemia during pregnancy, < 2 years inter-pregnancy interval and cigarette smoking during pregnancy. Health care providers should screen and sensitize mothers on the risk factors of LBW during antenatal sessions.
Insecticide resistance to insect growth regulators, avermectins, spinosyns and diamides in Culex quinquefasciatus in Saudi Arabia
Authors: Hafez Abdulwahab M. , Abbas Naeem
Published: October 2021

Background

Culex quinquefasciatus is not only a biting nuisance but also an important vector of fatal diseases. In Saudi Arabia, management measures to control this mosquito and thereby prevent associated disease transmission have focused on insecticides. Nevertheless, information on the resistance status of C. quinquefasciatus is insufficient, especially concerning insecticides containing novel classes of insecticides.

Methods

We evaluated six insecticides belonging to four classes of insecticides (insect growth regulators [3], avermectins [1], diamides [1] and spinosyns [1]) for toxicity and resistance in eight C. quinquefasciatus populations (from Ishbiliya, Al-Masfa, Al-Masanie, Al-Washlah, Al-Nakhil, Irqah, Al-Suwaidi and Al-Ghanemiya) following World Health Organisation protocols.

Results

Resistance status ranging from susceptibility/low resistance to high resistance, in comparison with the susceptible strain, was detected for cyromazine in the eight C. quinquefasciatus populations: Ishbiliya (resistance ratio [RR] = 3.33), Al-Masfa (RR = 4.33), Al-Masanie (RR = 3.67), Al-Washlah (RR = 2.33), Al-Nakhil (RR = 5.33), Irqah (RR = 7.00), Al-Suwaidi (RR = 21.33) and Al-Ghanemiya (RR = 16.00). All C. quinquefasciatus populations exhibited a high level of resistance to diflubenzuron (RR = 13.33–43.33), with the exception of Al-Nakhil which exhibited moderate resistance (RR = 10.00). Susceptibility/low resistance to high resistance was observed for triflumuron in the eight C. quinquefasciatus populations: Ishbiliya (RR = 0.50), Al-Ghanemiya (RR =  3.00), Al-Suwaidi (RR =  10.00), Al-Masfa (RR =  5.00), Al-Masanie (RR =  10.00), Al-Nakhil (RR =  5.00), Irqah (RR =  5.00) and Al-Washlah (RR =  15.00). Susceptibility/low resistance was assessed for abamectin, chlorantraniliprole and spinosad in all C. quinquefasciatus populations, with RR ranges of 0.25–3.50, 0.17–2.19, and 0.02–0.50, respectively. However, the population collected from Irqah showed high resistance to chlorantraniliprole (RR = 11.93).

Conclusions

The detection of widespread resistance to insect growth regulators in C. quinquefasciatus highlights an urgent need to establish integrated vector management strategies. Our results may facilitate the selection of potent insecticides for integrated vector management programmes for C. quinquefasciatus.

Graphical Abstract