bluuebunny/crossref_metadata_2025 huggingface dataset:
The quality of Cochrane systematic reviews of acupuncture: an overview
Authors: Ji Zhaochen , Zhang Junhua , Menniti-Ippolito Francesca , Massari Marco , Fauci Alice Josephine , Li Na , Yang Fengwen , Zhang Mingyan
Published: October 2020

Background

Many systematic reviews of clinical trials on acupuncture were performed within the Cochrane Collaboration, the evidence-based medicine (EBM) most recognized organization. Objective of the article was to systematically collect and identify systematic reviews of acupuncture published in the Cochrane Library and assess their quality from a methodological perspective.

Methods

A comprehensive literature search was performed in the Cochrane Database of Systematic Reviews to identify the reviews of acupuncture conducted until June 2019. The methodological quality of the included reviews was assessed using the AMSTAR 2 checklist, an evaluation tool for systematic reviews.

Results

Out of a total of 126 eligible reviews, 50 systematic reviews were included. According to the AMSTAR 2, 52% of Cochrane Systematic Reviews (CSRs) were of low quality, due to the presence of one or more weaknesses in at least one of the domains defined as critical for the methodological quality assessment. The less satisfied critical domain was inadequate investigation and discussion of publication bias. Declaration of potential sources of conflict of interest, and funding of the authors of the review and of the included studies were other important weaknesses.

Conclusions

The main methodological flaws in the included CSRs were related to topics of relatively new concern in the conduction of systematic reviews of the literature. However, both, lack of attention about retrieval of negative studies, and statements about conflict of interests are crucial point for the evaluation of therapeutic interventions according to EBM methodology.
Higher levels of the soluble receptor for advanced glycation end products and lower levels of the extracellular newly identified receptor for advanced glycation end products were associated with lipid-lowering drugs in patients with type 1 diabetes: a comparative cross-sectional study
Authors: Melin Eva O. , Dereke Jonatan , Hillman Magnus
Published: October 2020

Background

The receptors for advanced glycation end products (RAGE) are increased in atherosclerotic plaques. Soluble (s)RAGE decreases, whereas the extracellular newly identified receptor for advanced glycation end products (EN-RAGE) increases inflammatory responses mediated by RAGE. The aims were to explore whether sRAGE, EN-RAGE and the EN-RAGE/sRAGE ratio, were associated with the use of lipid-lowering drugs (LLD) and/or antihypertensive drugs (AHD) in patients with type 1 diabetes (T1D).

Methods

Cross-sectional design. T1D patients were consecutively recruited from one diabetes clinic. Blood samples were collected, supplemented with data from electronic health records. sRAGE and EN-RAGE were analysed by enzyme linked immunosorbent assays. An EN-RAGE/sRAGE ratio was calculated. Adjustments were performed with inflammatory and metabolic variables, s-creatinine, depression, smoking, physical inactivity, medication, and cardiovascular complications. Multiple regression analyses were performed.

Results

In this study 283 T1D patients (men 56%, 18–59 years) were included. One-hundred and thirty LLD users compared to 153 non-users had lower levels of the EN-RAGE/sRAGE ratio (P = 0.009), and 89 AHD users compared to 194 non-users had lower levels of sRAGE (P = 0.031). The use of LLD (inversely) (B coefficient − 0.158, P = 0.033) and the use of AHD (B coefficient 0.187, P = 0.023) were associated with the EN-RAGE/sRAGE ratio. sRAGE (Lg10) (per unit) (adjusted odds ratio (AOR) = 3.5, 95% CI = 1.4–9.1, P = 0.009), EN-RAGE (Lg10) (per unit) (inversely) (AOR 0.4, 95% CI = 0.2–1.0, P = 0.046), age (P <  0.001), and triglycerides (P <  0.029), were associated with LLD. sRAGE (Lg10) (per unit) (inversely) (AOR = 0.2, 95% CI = 0.1–0.5, P = 0.001), diabetes duration, triglycerides, s-creatinine, and systolic BP (all P values < 0.043), were associated with AHD.

Conclusions

Higher sRAGE levels and lower EN-RAGE levels were linked to the use of LLD, whereas lower sRAGE levels were linked to the use of AHD. No other variables but the use of LLD and the use of AHD were linked to the EN-RAGE/sRAGE ratio. This may be of major importance as sRAGE is an inhibitor and EN-RAGE is a stimulator of inflammatory processes mediated by RAGE.
Validity of the older people quality of life-7 domains (OQoL-7) scale
Authors: Henchoz Yves , Büla Christophe , Guessous Idris , Goy René , Dupuis Marc , Santos-Eggimann Brigitte
Published: October 2020

Background

The Older people Quality of Life-7 domains (OQoL-7) is a 28-item multidimensional questionnaire developed to measure community-dwelling older people’s QoL. The OQoL-7 assesses both importance of and satisfaction in seven QoL domains (Material resources; Close entourage; Social and cultural life; Esteem and recognition; Health and mobility; Feeling of safety; and Autonomy). This study aimed to investigate concurrent and construct validity of the OQoL-7. A secondary aim was to compare different methods of weighting participants’ ratings of satisfaction according to their individual ratings of importance, as compared to the OQoL-7 total score (unweighted).

Methods

Data came from the first and second samples of the Lausanne cohort 65+ study, assessed at the same age of 72–77 years in 2011 (N = 1117) and 2016 (N = 1091), respectively. To assess concurrent validity, the OQoL-7 was compared to other measures of the same concept (single QoL item) or related concepts (self-rated health, SF-12). Construct validity was tested by comparing subscores in the seven QoL domains in the presence and absence of two stressful events during the preceding year (financial difficulties and relationship difficulties). The effect of importance weighting was assessed using moderated regression analysis.

Results

The OQoL-7 total score was significantly associated with the single QoL item (Spearman’s rho 0.46), self-rated health (Spearman’s rho 0.34), SF-12 physical (Spearman’s rho 0.22) and mental (Spearman’s rho 0.28) component scores. Large differences (Cohen’s d > 0.8) were observed in the presence or absence of stressful events in the expected QoL domains: “Material resources” in the presence or absence of “Financial difficulties” (Cohen’s d 1.34), and “Close entourage” in the presence or absence of “Relationship difficulties” (Cohen’s d 0.84). Importance weighting resulted in a very small improvement in the prediction of the single QoL item (ΔR2 0.018). All results were highly consistent across 2011 and 2016 samples.

Conclusions

The OQoL-7 showed adequate concurrent and construct validity in two samples of older people. In future studies, the decision to use weighted or unweighted scores will depend on the priority given to either optimizing the prediction of QoL or limiting the burden on respondents and the amount of missing data.
A comparison between different anti-retroviral therapy regimes on soluble inflammation markers: a pilot study
Authors: Maritati Martina , Alessandro Trentini , Zanotta Nunzia , Comar Manola , Bellini Tiziana , Sighinolfi Laura , Contini Carlo
Published: October 2020

Background

Although HIV-related deaths have decreased dramatically following the introduction of antiretroviral therapy (ART), HIV infection itself causes increased morbidity and mortality for both non-AIDS-related events or chronic inflammation and immune activation. The use of certain antiretroviral drugs can contribute to this process.

Methods

We investigated 26 potential biomarkers in serum samples from HIV-1 infected patients virologically suppressed under ART. The main objective of our study was to evaluate if virological suppression achieved with a triple drug regimen containing tenofovir disoproxil fumarate co-formulated with emtricitabine (TDF/FTC) as backbone, could correlate with a better immunological and inflammatory profile in relation to the third class of antiretroviral drug administered. The eligible patients were then divided into 3 groups in relation to the third drug associated with TDF/FTC: nucleoside reverse transcriptase inhibitors (NNRTI) (Group 1, n = 16), protease inhibitors (PI) (Group 2, n = 17) and integrase inhibitors (INI) (Group 3, n = 16).

Results

Inflammatory cytokines and chemokines were more represented in Group 2 than in Group 3 (IL-1Ra,p = 0.013; IL-12p70p = 0.039; TNF-αp = 0.041; IL-8,p = 0.027; MIP1 β,p = 0.033). Eotaxin showed lower levels in Group 1 compared to Group 2 (p = 0.010), while IP-10 was significantly lower in Group 1 compared to both Group 2 and Group 3 (p = 0.003 and p = 0.007, respectively).

Conclusions

Our results seem to discourage the administration of PI as a third drug in a virologically effective antiretroviral regimen, as its use is linked to the detection of higher levels of pro-inflammatory mediators in comparison with INI and NNRTI.
LC–MS/MS-based in vitro and in vivo investigation of blood–brain barrier integrity by simultaneous quantitation of mannitol and sucrose
Authors: Noorani Behnam , Chowdhury Ekram Ahmed , Alqahtani Faleh , Ahn Yeseul , Patel Dhavalkumar , Al-Ahmad Abraham , Mehvar Reza , Bickel Ulrich
Published: October 2020

Background

Understanding the pathophysiology of the blood brain–barrier (BBB) plays a critical role in diagnosis and treatment of disease conditions. Applying a sensitive and specific LC–MS/MS technique for the measurement of BBB integrity with high precision, we have recently introduced non-radioactive [13C12]sucrose as a superior marker substance. Comparison of permeability markers with different molecular weight, but otherwise similar physicochemical properties, can provide insights into the uptake mechanism at the BBB. Mannitol is a small hydrophilic, uncharged molecule that is half the size of sucrose. Previously only radioactive [3H]mannitol or [14C]mannitol has been used to measure BBB integrity.

Methods

We developed a UPLC–MS/MS method for simultaneous analysis of stable isotope-labeled sucrose and mannitol. The in vivo BBB permeability of [13C6]mannitol and [13C12]sucrose was measured in mice, using [13C6]sucrose as a vascular marker to correct for brain intravascular content. Moreover, a Transwell model with induced pluripotent stem cell-derived brain endothelial cells was used to measure the permeability coefficient of sucrose and mannitol in vitro both under control and compromised (in the presence of IL-1β) conditions.

Results

We found low permeability values for both mannitol and sucrose in vitro (permeability coefficients of 4.99 ± 0.152 × 10−7and 3.12 ± 0.176 × 10−7cm/s, respectively) and in vivo (PS products of 0.267 ± 0.021 and 0.126 ± 0.025 µl g−1min−1, respectively). Further, the in vitro permeability of both markers substantially increased in the presence of IL-1β. Corrected brain concentrations (Cbr), obtained by washout vs. vascular marker correction, were not significantly different for either mannitol (0.071 ± 0.007 and 0.065 ± 0.009 percent injected dose per g) or sucrose (0.035 ± 0.003 and 0.037 ± 0.005 percent injected dose per g). These data also indicate that Cbrand PS product values of mannitol were about twice the corresponding values of sucrose.

Conclusions

We established a highly sensitive, specific and reproducible approach to simultaneously measure the BBB permeability of two classical low molecular weight, hydrophilic markers in a stable isotope labeled format. This method is now available as a tool to quantify BBB permeability in vitro and in vivo in different disease models, as well as for monitoring treatment outcomes.
Comparative carcinogenicity study of a thick, straight-type and a thin, tangled-type multi-walled carbon nanotube administered by intra-tracheal instillation in the rat
Authors: Saleh Dina Mourad , Alexander William T. , Numano Takamasa , Ahmed Omnia Hosny Mohamed , Gunasekaran Sivagami , Alexander David B. , Abdelgied Mohamed , El-Gazzar Ahmed M. , Takase Hiroshi , Xu Jiegou , Naiki-Ito Aya , Takahashi Satoru , Hirose Akihiko , Ohnishi Makoto , Kanno Jun , Tsuda Hiroyuki
Published: October 2020

Background

Multi-walled carbon nanotubes can be divided into two general subtypes: tangled and straight. MWCNT-N (60 nm in diameter) and MWCNT-7 (80–90 nm in diameter) are straight-type MWCNTs, and similarly to asbestos, both are carcinogenic to the lung and pleura when administered to rats via the airway. Injection of straight-type MWCNTs into the peritoneal cavity also induces the development of mesothelioma, however, injection of tangled-type MWCNTs into the peritoneal cavity does not induce carcinogenesis. To investigate these effects in the lung we conducted a 2-year comparative study of the potential carcinogenicities of a straight-type MWCNT, MWCNT-A (approximately 150 nm in diameter), and a tangled-type MWCNT, MWCNT-B (7.4 nm in diameter) after administration into the rat lung. Crocidolite asbestos was used as the reference material, and rats administered vehicle were used as the controls. Test materials were administered by intra-Tracheal Intra-Pulmonary Spraying (TIPS) once a week over a 7 week period (8 administrations from day 1 to day 50), followed by a 2-year observation period without further treatment. Rats were administered total doses of 0.5 or 1.0 mg MWCNT-A and MWCNT-B or 1.0 mg asbestos.

Results

There was no difference in survival between any of the groups. The rats administered MWCNT-A or asbestos did not have a significant increase in bronchiolo-alveolar hyperplasia or tumors in the lung. However, the rats administered MWCNT-B did have significantly elevated incidences of bronchiolo-alveolar hyperplasia and tumors in the lung: the incidence of bronchiolo-alveolar hyperplasia was 0/20, 6/20, and 9/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively, and the incidence of adenoma and adenocarcinoma combined was 1/19, 5/20, and 7/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively. Malignant pleural mesothelioma was not induced in any of the groups.

Conclusions

The results of this initial study indicate that tangled-type MWCNT-B is carcinogenic to the rat lung when administered via the airway, and that straight-type MWCNT-A did not have higher carcinogenic potential in the rat lung than tangled-type MWCNT-B.
Comparison of methods for quantifying primordial follicles in the mouse ovary
Authors: Sarma Urooza C. , Winship Amy L. , Hutt Karla J.
Published: October 2020

Background

Accurate evaluation of primordial follicle numbers in mouse ovaries is an essential endpoint for studies investigating how endogenous and exogenous insults, such as maternal aging and chemotherapy, impact the ovarian reserve. In this study, we compared and contrasted two methods for counting healthy primordial follicles following exposure to cyclophosphamide (75 mg/kg), a well-established model of follicle depletion. The first was the fractionator/optical dissector technique, an unbiased, assumption-free stereological approach for quantification of primordial follicle numbers. While accurate, highly reproducible and sensitive, this method relies on specialist microscopy equipment and software, requires specific fixation, embedding and sectioning parameters to be followed, and is largely a manual process that is tedious and time-consuming. The second method was the more widely used serial section and direct count approach, which is relatively quick and easy. We also compared the impacts of different fixatives, embedding material and section thickness on the overall results for each method.

Results

Direct counts resulted in primordial follicle numbers that were significantly lower than those obtained by stereology, irrespective of fixation and embedding material. When applied to formalin fixed tissue, the direct count method did not detect differences in follicle numbers between saline and cyclophosphamide treated groups to the same degree of sensitivity as the gold standard stereology method (referred to as the Reference standard). However, when Bouin’s fixative was used, direct counts and stereology were comparable in their ability to detect follicle depletion caused by cyclophosphamide.

Conclusions

This work indicates that the direct count method can produce similar results to stereology when Bouin’s fixative is used instead of formalin. The findings presented here will assist others to select the most appropriate experimental approach for accurate follicle enumeration, depending on whether the primary objective of the study is to determine absolute primordial follicle numbers or relative differences between groups.
Morphological and molecular characterization of Sarcocystis wenzeli in chickens (Gallus gallus) in China
Authors: Pan Jing , Ma Chunli , Huang Zhumei , Ye Yulong , Zeng Hongxia , Deng Shuangsheng , Hu Junjie , Tao Jianping
Published: October 2020

Background

There has been considerable confusion concerning the number and classification of Sarcocystis spp. in chickens. Scarce nucleotide data of Sarcocystis spp. from chickens are provided in GenBank. The study aimed to investigate the morphological and molecular characteristics of Sarcocystis spp. found in chickens in China.

Methods

Tissues from 33 chickens were collected in 2019. Sarcocysts were observed using light (LM) and transmission electron microscopy (TEM). Individual sarcocysts from different chickens were selected for DNA extraction, and five loci, 18S rDNA, 28S rDNA, ITS1 region, the mitochondrial cox1 gene and the apicoplastic rpoB gene, were amplified from each sarcocyst, sequenced and analyzed.

Results

Only S. wenzeli was found in 14 of 33 (42.4%) chickens. Under LM, the sarcocysts were microscopic and exhibited palisade-like villar protrusions measuring 1.5–2.8 μm. Ultrastructurally, the sarcocyst wall contained numerous stubby hill-like villar protrusions. The protrusions included scattered microtubules, which extended from the tips of the protrusions into the ground substance. The five loci were successfully sequenced and the sequences deposited in GenBank. At 18S rDNA, ITS1 and cox1, the most similar sequences in GenBank were those of Sarcocystis sp. obtained from the brains of chickens, i.e. 99.9–100%, 98.1–98.5% and 99.3% identity, respectively. The five loci (18S rDNA, 28S rDNA, ITS1, cox1 and rpoB) showed different levels of interspecific sequence similarity with other closely related species of Sarcocystis (e.g. 99.8%, 99.0–99.2%, 89.3–89.7%, 98.5%, and 97.5%, respectively, with S. anasi). Phylogenetic analysis based on four of the loci (18S rDNA, cox1, rpoB and ITS1) revealed that S. wenzeli formed an independent clade with Sarcocystis spp. that utilize geese or ducks as intermediate hosts and canines as the known or presumed definitive host.

Conclusions

To our knowledge, the sequences of 28S rDNA and rpoB reported here constitute the first records of genetic markers of Sarcocystis spp. in chickens. Based on molecular analysis, S. wenzeli might be responsible for the neurological disease in chickens, and ITS1 and rpoB are more suitable for discriminating it from closely related Sarcocystis spp. Phylogenetic analysis revealed that S. wenzeli presents a close relationship with Sarcocystis spp. in geese or ducks.
Evidence of vector borne transmission of Salmonella enterica enterica serovar Gallinarum and fowl typhoid disease mediated by the poultry red mite, Dermanyssus gallinae (De Geer, 1778)
Authors: Cocciolo Giulio , Circella Elena , Pugliese Nicola , Lupini Caterina , Mescolini Giulia , Catelli Elena , Borchert-Stuhlträger Monika , Zoller Hartmut , Thomas Emmanuel , Camarda Antonio
Published: October 2020

Background

The poultry red mite Dermanyssus gallinae (De Geer, 1778) is a major ectoparasite of poultry. Infestations are found in most laying hen farms in Europe, and breeder flocks have also been reported to be affected. Mite infestation has detrimental effects on animal welfare, it causes significant economic losses, and, additionally, D. gallinae is often considered as a vector for pathogens. Despite suspicion of a close relationship between the poultry red mite and Salmonella enterica enterica serovar Gallinarum biovar Gallinarum (serovar Gallinarum), the causative agent of fowl typhoid disease (FT), there has been no definitive proof of mite-mediated transmission. Therefore, an investigation was conducted to determine if D. gallinae-mediated transmission of serovar Gallinarum could be demonstrated among four different hen groups.

Methods

Two groups of 8 hens (A and B) were experimentally infected with serovar Gallinarum in two isolators. After 7 days, when birds showed signs of FT, about 25,000 mites were introduced. After 3 days, mites were harvested and used to infest two other hen groups of 8 (C and D), in two separate isolators. The health status of hens was constantly monitored; detection and quantification of serovar Gallinarum were performed by PCR and qPCR from mites and organs of dead hens. The maximum likelihood estimation of the infection rate and mite vectorial capacity were calculated.

Results

Clinical disease was observed in groups infected with serovar Gallinarum (A and B) and in hens of groups C and D infested with mites harvested from the isolators containing groups A and B. In all four groups, serovar Gallinarum was detected from liver, spleen, ovary, and cecum of hens, thus confirming the diagnosis of FT. Mite analysis demonstrated the presence of the pathogen, with an estimated infection rate ranging between 13.72 and 55.21 infected per thousand mites. Vectorial capacity was estimated to be 73.79.

Conclusions

Mites harvested from birds infected with serovar Gallinarum were shown to carry the mite, and then to transfer serovar Gallinarum to isolated groups of pathogen-free birds that subsequently showed signs of FT. Mite vectorial capacity was high, demonstrating that D. gallinae should be considered an effective vector of FT.
The role of brachytherapy for margin control in oral tongue squamous cell carcinoma
Authors: Ianovski Ilia , Mlynarek Alex M. , Black Martin J. , Bahoric Boris , Sultanem Khalil , Hier Michael P.
Published: October 2020

Background

The aim of this study is to assess the feasibility and effectiveness of using peri-operative brachytherapy (BRTx) for positive/narrow margins present post primary surgical resection of oral tongue squamous cell carcinoma (OTSCC).

Methods

Prospective single-centre study of patients with OTSCC (T1–3, N0–3, M0) treated with resection of primary tumour ± regional nodal resection and intra-operative insertion of BRTx catheters. BRTx was administered twice daily at 40.8Gy/12Fr for ‘Positive’ (≤2 mm) margins, at 34Gy/10Fr for ‘Narrow’ (2.1-5 mm) margins, and not given for ‘Clear’ (> 5 mm) margins over the course of 5–6 days, 3–5 days post operatively.

Results

Out of 55 patients recruited 41 patients (74.6%) were treated with BRTx, as 12 patients had clear margins and 2 patients had unfavourable tumour anatomy for catheter insertion. EBRTx was avoided in 64.3% of patients. Overall Survival (OS) at 3 and 5 years was 75.6 and 59.1% respectively, while Disease Specific Survival (DSS) was 82.3 and 68.6% at 3 and 5 years respectively. Recurrence and survival outcomes were not associated with margin status or the use of or specific dose of BRTx on Cox regression analysis. Acute and late toxicity secondary to BRTx was minimal.

Conclusions

The use of BRTx after primary OTSCC resection with positive/narrow margins ± EBRTx to the neck ± CTx achieves outcomes comparable to traditional treatment of surgery followed by re-resection or EBRTx ± CTx. Morbidity associated with oral cavity EBRTx or secondary resection and reconstruction is thus avoided. Both acute and late toxicity rates are low and compare favourably with other BRTx OTSCC studies.

Trial registration

Retrospectively registered. https://www.mcgill.ca/rcr-rcn/files/rcr-rcn/2017.06.05_rcn_hn.pdf .

Level of evidence

4

Graphical abstract
Logistics integration in the supply chain: a resource dependence theory perspective
Authors: Kim Sung Tae , Lee Hong-Hee , Hwang Taewon
Published: October 2020

Firms have strategically used cooperative linkages to establish competitiveness. In this study, we incorporated the resource dependency theory view to assess how trust, satisfaction, and commitment affect firms’ decisions on logistics integration. Also, we examined the link between logistics integration and supply chain performance. The study collected data from 250 South Korean manufacturers for analysis. The results revealed positive impacts of trust, satisfaction, and commitment on logistics integration between manufacturing firms and logistics service providers that enhances logistics service capabilities of the firms. Furthermore, our study showed that building a strategic relationship for logistics services helps the manufacturing firms improve their business and operations performances in their supply chain. Implications and suggestions for future research are discussed.
Variation in Botryosphaeriaceae from Eucalyptus plantations in YunNan Province in southwestern China across a climatic gradient
Authors: Li Guoqing , Slippers Bernard , Wingfield Michael J. , Chen Shuaifei
Published: October 2020

The Botryosphaeriaceae accommodates many important pathogens of woody plants, including Eucalyptus. Recently, Botryosphaeriaceae were isolated from diseased plant parts from surveys of Eucalyptus plantations in the YunNan Province, China. The aims of this study were to identify these Botryosphaeriaceae isolates and to evaluate their pathogenicity to Eucalyptus. A total of 166 isolates of Botryosphaeriaceae were obtained from six regions in the YunNan Province, of which 76 were from Eucalyptus urophylla × E. grandis hybrids, 49 from E. globulus trees, and 41 isolates were from other unknown Eucalyptus species or hybrids. Isolates were identified by comparing DNA sequences of the internal transcribed spacer ribosomal RNA locus (ITS), partial translation elongation factor 1-alpha (tef1), β-tubulin 2 (tub2) and DNA-directed RNA polymerase II subunit (rpb2) genes, and combined with their morphological characteristics. Eleven species were identified, including Botryosphaeria fusispora, B. wangensis, Lasiodiplodia pseudotheobromae, Neofusicoccum kwambonambiense, N. parvum, and six novel species described as B. puerensis, N. dianense, N. magniconidium, N. ningerense, N. parviconidium and N. yunnanense. The dominant species across the regions were N. yunnanense, N. parvum and B. wangensis, representing 31.3, 25.3 and 19.9% of the total isolates, respectively. Species diversity and composition changed across the different climatic zones, despite their relatively close geographic proximity and the fact that some of the species have a global distribution. All the Botryosphaeriaceae species were pathogenic to one-year-old plants of an E. urophylla × E. grandis clone and E. globulus seed-derived plants, but showed significant inter- and intra-species variation in aggressiveness amongst isolates. The study provides a foundation for monitoring and management of Botryosphaeriaceae through selection and breeding of Eucalyptus in the YunNan Province of southwestern China.
Believing that transferring more embryos will result in increased pregnancy rates: a flawed concept: a SWOT analysis
Authors: Dahan Michael H. , Tannus Samer
Published: October 2020

A belief exists that transferring multiple embryos can improve pregnancy rates. However, this concept is flawed. Multiple factors affect outcomes when transferring embryos, endometrial receptivity, and rates of aneuploidy among them. In this article, we will discuss how factors can affect outcomes at IVF that are independent of the number of embryos transferred. It is important to understand the role of accessory factors on pregnancy rates to be able to counsel patients as per the number of embryos that should be transferred. An understanding of this concept will also lead to a realistic understanding of how multiple embryo transfers may result in better cumulative pregnancy rates than a single transfer of multiple embryos. Finally, we will present a SWOT analysis diagram to help guide clinical decision-making.
A method for modeling multiscale geomechanical effects in the stimulated rock volume
Authors: Busetti Seth
Published: October 2020

I have developed a workflow to efficiently simulate geomechanical effects in the stimulated rock volume (SRV) by including regional geologic structures such as faults and folds as well as high-resolution-oriented mechanical stratigraphy. The motivation is that the local model used for hydraulic fracture analysis should include macroscale 3D geomechanical effects derived from regional tectonic and seismic data. A practical computational strategy is developed to link multiple 3D geomechanical models derived at different scales and their associated stress effects. I apply the workflow to a synthetic reservoir problem composed of a tectonic-scale structural framework model with three embedded mechanical stratigraphic models representing three stimulated vertical wells. I first combine regional stresses solved with 3D finite-element analysis with perturbation stresses from elastic dislocation modeling using elastic superposition concepts. I then apply the macroscale stress effects as unique boundary conditions to an embedded finite-element submodel, a mesoscale stratigraphic model representing the SRV allowing for resolution of variable stress amplification, and stress rotation in geologic sublayers. Finally, I conduct hydraulic-fracture simulations within the SRV models. The simulated hydraulic fractures are controled by the structural position and mechanical stratigraphy. Closest to the back limb of the main structural anticline, hydraulic fractures tend to be height-restricted, and in some realizations, fractures propagate horizontally. Adjacent to the fold and a fault, where differential stresses are elevated, fracture growth is the most unconstrained in height and length. Results suggest that this multiscale approach can be applied to better predict and understand behaviors related to unconventional reservoir stimulation. The workflow could easily be modified for other operational problems and geologic settings.
Equivalence Randomized Trial to Compare Treatment on the Basis of Sentinel Node Biopsy Versus Neck Node Dissection in Operable T1-T2N0 Oral and Oropharyngeal Cancer
Authors: Garrel Renaud , Poissonnet Gilles , Moyà Plana Antoine , Fakhry Nicolas , Dolivet Gilles , Lallemant Benjamin , Sarini Jérôme , Vergez Sebastien , Guelfucci Bruno , Choussy Olivier , Bastit Vianney , Richard Fanny , Costes Valérie , Landais Paul , Perriard Françoise , Daures Jean Pierre , de Verbizier Delphine , Favier Valentin , de Boutray Marie
Published: October 2020

PURPOSE

Sentinel node (SN) biopsy is accurate in operable oral and oropharyngeal cT1-T2N0 cancer (OC), but, to our knowledge, the oncologic equivalence of SN biopsy and neck lymph node dissection (ND; standard treatment) has never been evaluated.

METHODS

In this phase III multicenter trial, 307 patients with OC were randomly assigned to (1) the ND arm or (2) the SN arm (experimental arm: biopsy alone if negative, or followed by ND if positive, during primary tumor surgery). The primary outcome was neck node recurrence-free survival (RFS) at 2 years. Secondary outcomes were 5-year neck node RFS, 2- and 5-year disease-specific survival (DSS), and overall survival (OS). Other outcomes were hospital stay length, neck and shoulder morbidity, and number of physiotherapy prescriptions during the 2 years after surgery.

RESULTS

Data on 279 patients (139 ND and 140 SN) could be analyzed. Neck node RFS was 89.6% (95% CI, 0.83% to 0.94%) at 2 years in the ND arm and 90.7% (95% CI, 0.84% to 0.95%) in the SN arm, confirming the equivalence with P < .01. The 5-year RFS and the 2- and 5-year DSS and OS were not significantly different between arms. The median hospital stay length was 8 days in the ND arm and 7 days in the SN arm ( P < .01). The functional outcomes were significantly worse in the ND arm until 6 months after surgery.

CONCLUSION

This study demonstrated the oncologic equivalence of the SN and ND approaches, with lower morbidity in the SN arm during the first 6 months after surgery, thus establishing SN as the standard of care in OC.
Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial
Authors: Lan Chunyan , Shen Jingxian , Wang Yin , Li Jundong , Liu Zhimin , He Mian , Cao Xinping , Ling Jiayu , Huang Jiaming , Zheng Min , Zou Guorong , Yan Haowen , Liu Qing , Yang Fan , Wei Wei , Deng Yanhong , Xiong Ying , Huang Xin
Published: October 2020

PURPOSE

Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer.

METHODS

This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety.

RESULTS

Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%).

CONCLUSION

Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.
X-Linked Hypophosphatemia: A New Era in Management
Authors: Dahir Kathryn , Roberts Mary Scott , Krolczyk Stan , Simmons Jill H
Published: October 2020

X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive musculoskeletal disease that often causes pain and short stature, as well as decreased physical function, mobility, and quality of life. Hypophosphatemia in XLH is caused by loss of function mutations in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene, resulting in excess levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23), which leads to renal phosphate wasting and decreased serum 1,25-dihydroxyvitamin D production. Historically, treatment options were limited to oral phosphate and active vitamin D analogues (conventional management) dosed several times daily in an attempt to improve skeletal mineralization by increasing serum phosphorus. The recent approval of burosumab, a fully human monoclonal antibody to FGF23, has provided a new, targeted treatment option for patients with XLH. This review summarizes our current understanding of XLH, the safety and efficacy of conventional management and burosumab, existing recommendations for managing patients, and unanswered questions in the field.
Formation of an Intraoperative Educational Curriculum for Anesthesiology Residents Using a Systematic Approach
Authors: Walsh Daniel P. , Neves Sara E. , Wong Vanessa T. , Mitchell John D.
Published: October 2020

Anesthesiology residents spend most of their training in operating rooms, but intraoperative teaching is often unstructured. Needs assessment indicated a need to incorporate a more evidence-based approach to education and improvement of our methods of introducing residents to primary anesthesiology literature. Kern’s 6-step approach to curriculum development was used to create a robust and innovative curriculum to increase both the evidence-based component of our curriculum and the amount of educational intraoperative discussion among trainees and faculty. Our curriculum uses a structured topic outline, an e-journal club, and other relevant resources to facilitate discussion of the topics.
Sexual functioning as predictor of depressive symptoms and life satisfaction in females with Polycystic Ovary Syndrome (PCOS)
Authors: Shakeel Muneeba , Ashraf Farzana , Wajid Amina
Published: October 2020

Background & Objective: PCOS is the one of the frequently diagnosed endocrine syndrome in Pakistani women. However, little attention has been devoted to empirical investigation of the role of sexual dysfunction in developing depressive symptoms and reducing life satisfaction. Our objective was to determine the contribution of Sexual dysfunction in developing depressive symptoms and life dissatisfaction in females diagnosed with PCOS.

Methods: This correlation study was carried out from 1st September 2019 to 15th February 2020 at COMSATS University Islamabad, Lahore Campus. A sample of 60 women with PCOS between reproductive age 18 – 38 years (Mage = 27.86, SD = 4.58) was selected through purposive sampling technique from the government hospitals of Lahore, Pakistan. The participants responded to a Demographic Information Form, Female Sexual Functioning Index, Siddiqui Shah Depression and Life Satisfaction Scale.

Results: Correlation analysis revealed significant positive link of sexual dysfunction with depressive symptoms and negative link with life satisfaction level. Further, regression analysis revealed sexual functioning as significant predictor of depressive symptoms only.

Conclusion: Sexual dysfunction play a major role in general mental health of females, therefore, screening and identification as well as preventive measure need to be introduced at early level of development. In addition, current study findings suggest that once females are diagnosed with PCOS, they should be provided sufficient counselling services in order to deal with depressive symptoms and feeling of low life satisfaction. Further, targeted interventions and counselling services may also facilitate in optimising patient care.

doi: https://doi.org/10.12669/pjms.36.7.2562

How to cite this:Shakil M, Ashraf F, Wajid A. Sexual functioning as predictor of depressive symptoms and life satisfaction in females with Polycystic Ovary Syndrome (PCOS). Pak J Med Sci. 2020;36(7):1500-1504. doi: https://doi.org/10.12669/pjms.36.7.2562

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ποιές είναι οι αντιλήψεις εκπαιδευτικών των γυμνασίων για τη χρήση της φορητής τεχνολογίας στις τάξεις;
Authors: Νικολοπούλου Κλεοπάτρα , Κουσλόγλου Μανόλης
Published: October 2020

Έρευνες αναφέρουν την ολοένα αυξανόμενη χρήση των ψηφιακών φορητών συσκευών (φορητής τεχνολογίας) και την υψηλή τους δημοφιλία μεταξύ των νέων/εφήβων. Η φορητή τεχνολογία έχει τη δυναμική να υποστηρίξει τη φορητή μάθηση στις τάξεις (υπό προϋποθέσεις), ενώ οι απόψεις των εκπαιδευτικών αποτελούν ένα σημαντικό παράγοντα που επηρεάζει την αποτελεσματικότητα της μάθησης. Η εργασία αυτή παρουσιάζει εμπειρικά δεδομένα αναφορικά με τις αντιλήψεις και τις απόψεις εκπαιδευτικών Β’θμιας εκπαίδευσης για τη χρήση της φορητής τεχνολογίας (tablet και κινητών τηλεφώνων) στις τάξεις και επικεντρώνεται στα πλεονεκτήματα, τα εμπόδια και τους ενδοιασμούς τους. Στην έρευνα συμμετείχαν 32 εκπαιδευτικοί από δύο Γυμνάσια της Καβάλας και οι απόψεις τους καταγράφηκαν με τη χρήση ερωτηματολογίου. Τα πλεονεκτήματα χρήσης που δηλώθηκαν από τους περισσότερους εκπαιδευτικούς αφορούν το διαδραστικό και ευχάριστο μάθημα, την κινητοποίηση των μαθητών και την ευκαιρία εξοικείωσής τους με την τεχνολογία. Ως κύριο εμπόδιο δηλώθηκε η έλλειψη εξοπλισμού αλλά και η ισχύουσα νομοθεσία για τη χρήση κινητών και tablet. Οι ενδοιασμοί των εκπαιδευτικών αφορούν την τυχόν παραβατική συμπεριφορά των μαθητών, τη δυσκολία ελέγχου τους, τη φασαρία στην τάξη και την απόσπαση της προσοχής των μαθητών. Συζητιούνται συνέπειες, προτάσεις για την επιμόρφωση των εκπαιδευτικών, την πολιτική του σχολείου και ευρύτερα την εκπαιδευτική πολιτική.
Eξ αποστάσεως διδασκαλία μέσω τηλεδιάσκεψης: οι επιδράσεις των τεχνολογικών παραγόντων
Authors: Αρμακόλας Στέφανος Ιωσήφ , Παναγιωτακόπουλος Xρήστος
Published: October 2020

Είναι αναμφισβήτητο πως, ένα απαραίτητο στοιχείο για τη διασφάλιση της αποτελεσματικότητας στην εξ αποστάσεως εκπαίδευση αποτελεί η επικοινωνία του εκπαιδευτή με κάθε εκπαιδευόμενο. Η τηλεδιάσκεψη αποτελεί ένα αξιόπιστο εργαλείο αμφίδρομης οπτικοακουστικής επικοινωνίας μεταξύ διδάσκοντα και διδασκομένων. Ωστόσο, η χρήση της προϋποθέτει τεχνολογικές γνώσεις.Σκοπός της παρούσας εργασίας να ερευνήσει τους τεχνολογικούς παράγοντες που επιδρούν σε εξ αποστάσεως διδασκαλία μέσω της τηλεδιάσκεψης και να διερευνήσει πιθανή συσχέτιση με την αποτελεσματικότητα του μαθησιακού περιβάλλοντος. Από τα αποτελέσματα της έρευνας φαίνεται ότι οι τεχνολογικοί παράγοντες έχουν επίδραση στην εξ αποστάσεως διδασκαλία μέσω της τηλεδιάσκεψης και σχετίζονται με τη μαθησιακή αποτελεσματικότητά της.
Case Report: Hemolysis in a G6PD-deficient patient, a dose-dependent effect of metformin
Authors: Irshad Yusra , Nadeem Mahum , Khan Usman , Tariq Ezza , Khakwani Aemen
Published: October 2020

Glucose-6-phosphate deficiency is an X-linked genetic disorder, which predisposes erythrocytes to oxidative stress, resulting in hemolysis. It is the most common enzymatic deficiency, and typically affects African, Asian, Mediterranean, and Middle Eastern lineages. It can be induced by some medications, chemicals, and foods. Metformin is an uncommon drug to cause hemolysis in G6PD-deficient patients.

We report a case of a 52-year old African American male with G6PD-related hemolysis secondary to toxic metformin accumulation with acute kidney injury (AKI). The patient was a type-2 diabetic and was taking metformin (500mg twice daily) for three years. He presented to the ER with nausea, vomiting, and diarrhea for last three days with severe hemodynamic instability. Labs revealed hemoglobin 15mg/dl, white blood count 28 mm3/L, creatinine 10 mg/dl, blood urea nitrogen 100 mg/dl, bicarbonate 7 mEq/L, lactic acid 17 mg/dl, pH 6.8, pCO2 21mmHg, metformin 41 mcg/ml, albumin-globulin 41. Severe sepsis protocol was activated; IV fluids 30ml/kg bolus and antibiotics were given. CT abdomen revealed colitis. The patient was started on continuous renal replacement therapy. The next day, the patient’s hemoglobin dropped to 12.6 mg/dl. A hemolytic panel was unswerving with hemolysis and G6PD levels reported low at 1.72. The patient improved with antibiotics, but the hemolysis continued. Metformin toxicity induced hemolysis was suspected. The patient’s hemoglobin dropped to 6g/dl and he received blood transfusions. His hemoglobin started to improve with hemodialysis sessions, as metformin levels started to normalize, emphasizing the fact that patient was clearing metformin.

Unlike most cases reported, in which hemolysis occurs within days to months of starting metformin, in our patient it occurred due to the cumulative effect of metformin because of the patient’s underlying AKI. This led us to propose that the hemolytic effect of metformin may not only be time-dependent but also dose-dependent.
Rapid Discrete Optimization via Simulation with Gaussian Markov Random Fields
Authors: Semelhago Mark , Nelson Barry L. , Song Eunhye , Wächter Andreas
Published: October 2020

Inference-based optimization via simulation, which substitutes Gaussian process (GP) learning for the structural properties exploited in mathematical programming, is a powerful paradigm that has been shown to be remarkably effective in problems of modest feasible-region size and decision-variable dimension. The limitation to “modest” problems is a result of the computational overhead and numerical challenges encountered in computing the GP conditional (posterior) distribution on each iteration. In this paper, we substantially expand the size of discrete-decision-variable optimization-via-simulation problems that can be attacked in this way by exploiting a particular GP—discrete Gaussian Markov random fields—and carefully tailored computational methods. The result is the rapid Gaussian Markov Improvement Algorithm (rGMIA), an algorithm that delivers both a global convergence guarantee and finite-sample optimality-gap inference for significantly larger problems. Between infrequent evaluations of the global conditional distribution, rGMIA applies the full power of GP learning to rapidly search smaller sets of promising feasible solutions that need not be spatially close. We carefully document the computational savings via complexity analysis and an extensive empirical study.

Summary of Contribution: The broad topic of the paper is optimization via simulation, which means optimizing some performance measure of a system that may only be estimated by executing a stochastic, discrete-event simulation. Stochastic simulation is a core topic and method of operations research. The focus of this paper is on significantly speeding-up the computations underlying an existing method that is based on Gaussian process learning, where the underlying Gaussian process is a discrete Gaussian Markov Random Field. This speed-up is accomplished by employing smart computational linear algebra, state-of-the-art algorithms, and a careful divide-and-conquer evaluation strategy. Problems of significantly greater size than any other existing algorithm with similar guarantees can solve are solved as illustrations.