bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential utility of physical function measures to improve the risk prediction of functional disability in community-dwelling older Japanese adults: a prospective study
Authors: Chen Tao , Honda Takanori , Chen Sanmei , Kishimoto Hiro , Kumagai Shuzo , Narazaki Kenji
Published: September 2021

Background

While gait speed, one-leg standing balance, and handgrip strength have been shown to be independent predictors for functional disability, it is unclear whether such simple measures of physical function contribute to improved risk prediction of functional disability in older adults.

Methods

A total of 1,591 adults aged ≥ 65 years and without functional disability at baseline were followed up for up to 7.9 years. Functional disability was identified using the database of Japan’s Long-term Care Insurance System. Maximum gait speed, one-leg standing time, and handgrip strength were measured at baseline. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association of physical function and functional disability incidence. The incremental predictive value of each physical function measure for risk prediction was quantified using the difference in overall C-statistic, category-free net reclassification improvement (NRI), and integrated discrimination improvement (IDI) index.

Results

During follow-up (median: 7.8 years), functional disability was identified in 384 participants. All of the physical function measures were inversely associated with the risk of functional disability, independent of potential confounding factors. The multivariable adjusted HRs (95 % CIs) for functional disability per one standard deviation increment of maximum gait speed, one-leg-standing time, and hand grip strength were 0.73 (0.65–0.83), 0.68 (0.59–0.79), and 0.72 (0.59–0.86), respectively. Incorporation of each of maximum gait speed, one-leg-stand time, and hand grip strength into a basic model with other risk factors significantly improved C-statistic from 0.770 (95 % CIs, 0.751–0.794) to 0.778 (0.759–0.803), 0.782 (0.760–0.805), and 0.775 (0.756–0.800), respectively (all p < 0.05). A model including all three measures had the highest C-statistic of 0.787 (0.765–0.810). The improvements in risk prediction were also confirmed by category-free NRI and IDI index.

Conclusions

Adding any of the three measures to a basic model with other known risk factors significantly improved the prediction of functional disability and addition of all three measures provided further improvement of the prediction in older Japanese adults. These data provide robust evidence to support the practical utility of incorporating these simple physical function measures into functional disability risk prediction tools.
Protocol of a prospective and multicentre China Teratology Birth Cohort (CTBC): association of maternal drug exposure during pregnancy with adverse pregnancy outcomes
Authors: Zhou Yangwen , Tao Jing , Wang Ke , Deng Kui , Wang Yanping , Zhao Jianxin , Chen Chunyi , Wu Tingxuan , Zhou Jiayuan , Zhu Jun , Li Xiaohong
Published: September 2021

Background

As reported, 27-93 % of pregnant women take at least one drug during pregnancy. However, drug exposure during pregnancy still lacks sufficient foetal safety evidence of human origin. It is urgent to fill the knowledge gap about medication safety during pregnancy for optimization of maternal disease treatment and pregnancy drug consultation.

Methods and analysis

The China Teratology Birth Cohort (CTBC) was established in 2019 and is a hospital-based open-ended prospective cohort study with the aim of assessing drug safety during pregnancy. Pregnant women who set up the pregnancy health records in the first trimester or who seek drug consultation regardless of gestational age in the member hospitals are recruited. Enrolled pregnant women need to be investigated four times, namely, 6–14 and 24–28 weeks of gestational age, before discharge after hospital delivery, and 28–42 days after birth.

Maternal medication exposure during pregnancy is the focus of the CTBC. For drugs, information on the type, name, and route of medication; start and end time of medication; single dose; frequency of medication; dosage form; manufacturer; and reason for medication is collected. The adverse pregnancy outcomes collected in the study include birth defects, stillbirth, spontaneous abortion, preterm birth, post-term birth, low birth weight, macrosomia, small for gestational age, large for gestational age and low Apgar score. CTBC uses an electronic questionnaire for data collection and a cloud system for data management. Biological samples are collected if informed consents are obtained. Multi-level logistic regression, mixed-effect negative binomial distribution regression and spline function regression are used to explore the effect of drugs on the occurrence of birth defects.

Discussion

The findings of the study will assist in further understanding the risk of birth defects and other adverse pregnancy outcomes associated with maternal drug exposure and developing the optimal treatment plans and drug counselling for pregnant women.

Trial registration

This study was approved by the Research Ethics Committee of the West China Second Hospital of Sichuan University and registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx, registration numberChiCTR1900022569).
Association of dietary intakes of vitamin B12, vitamin B6, folate, and methionine with the risk of esophageal cancer: the Japan Public Health Center-based (JPHC) prospective study
Authors: Khairan Paramita , Sobue Tomotaka , Eshak Ehab Salah , Zha Ling , Kitamura Tetsuhisa , Sawada Norie , Iwasaki Motoki , Inoue Manami , Yamaji Taiki , Shimazu Taichi , Iso Hiroyasu , Tsugane Shoichiro
Published: September 2021

Background

B vitamins and methionine are essential substrates in the one-carbon metabolism pathway involved in DNA synthesis and methylation. They may have essential roles in cancer development. We aimed to evaluate the associations of dietary intakes of vitamin B12, vitamin B6, folate, and methionine with the risk of esophageal cancer (EC) using data from the Japan Public Health Center-based Prospective Study.

Methods

We included 87,053 Japanese individuals who completed a food frequency questionnaire and were followed up from 1995–1998 to 2013 and 2015. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Cox proportional-hazard regression across quintiles of dietary intakes of B vitamins and methionine.

Results

After 1,456,678 person-years of follow-up, 427 EC cases were documented. The multivariable HR (95% CI) of incident EC in the highest versus lowest quintile of dietary intake of vitamin B12 was 1.75 (1.13–2.71; p-trend=0.01). Stratification analysis based on alcohol consumption showed that higher dietary intakes of vitamin B12 and methionine were associated with an increased risk of EC among never-drinkers; HRs (95% CIs) were 2.82 (1.18–6.74; p-trend=0.009; p-interaction=0.18) and 3.45 (1.32–9.06; p-trend=0.003; p-interaction 0.02) for vitamin B12 and methionine, respectively. Meanwhile, there was no association between vitamin B12 and methionine intake with the risk of EC among drinkers. There were no associations between dietary intake of folate or vitamin B6 and the risk of EC.

Conclusion

Dietary intake of vitamin B12 was positively associated with the risk of EC in the Japanese population.
Exposure to low intensity ultrasound removes paclitaxel cytotoxicity in breast and ovarian cancer cells
Authors: Amaya Celina , Luo Shihua , Baigorri Julio , Baucells Rogelio , Smith Elizabeth R. , Xu Xiang-Xi
Published: September 2021

Background

Paclitaxel (Taxol) is a microtubule-stabilizing drug used to treat several solid tumors, including ovarian, breast, non-small cell lung, and pancreatic cancers. The current treatment of ovarian cancer is chemotherapy using paclitaxel in combination with carboplatin as a frontline agent, and paclitaxel is also used in salvage treatment as a second line drug with a dose intensive regimen following recurrence. More recently, a dose dense approach for paclitaxel has been used to treat metastatic breast cancer with success.

Paclitaxel binds to beta tubulin with high affinity and stabilizes microtubule bundles. As a consequence of targeting microtubules, paclitaxel kills cancer cells through inhibition of mitosis, causing mitotic catastrophes, and by additional, not yet well defined non-mitotic mechanism(s).

Results

In exploring methods to modulate activity of paclitaxel in causing cancer cell death, we unexpectedly found that a brief exposure of paclitaxel-treated cells in culture to low intensity ultrasound waves prevented the paclitaxel-induced cytotoxicity and death of the cancer cells. The treatment with ultrasound shock waves was found to transiently disrupt the microtubule cytoskeleton and to eliminate paclitaxel-induced rigid microtubule bundles. When cellular microtubules were labelled with a fluorescent paclitaxel analog, exposure to ultrasound waves led to the disassembly of the labeled microtubules and localization of the signals to perinuclear compartments, which were determined to be lysosomes.

Conclusions

We suggest that ultrasound disrupts the paclitaxel-induced rigid microtubule cytoskeleton, generating paclitaxel bound fragments that undergo degradation. A new microtubule network forms from tubulins that are not bound by paclitaxel. Hence, ultrasound shock waves are able to abolish paclitaxel impact on microtubules.

Thus, our results demonstrate that a brief exposure to low intensity ultrasound can reduce and/or eliminate cytotoxicity associated with paclitaxel treatment of cancer cells in cultures.
Vitamin D status in full-term exclusively breastfed infants versus full-term breastfed infants receiving vitamin D supplementation in Thailand: a randomized controlled trial
Authors: Ruangkit Chayatat , Suwannachat Sukrit , Wantanakorn Pornchanok , Sethaphanich Napapailin , Assawawiroonhakarn Surapat , Dumrongwongsiri Oraporn
Published: September 2021

Background

Many international medical organizations recommend vitamin D supplementation for infants, especially exclusively breastfed infants. In Thailand, however, data regarding the vitamin D status in Thai infants are lacking. Such data would help to support physician decisions and guide medical practice.

Methods

Full-term, exclusively breastfed infants were randomized into two groups at 2 months of age to continue exclusive breastfeeding either without vitamin D supplementation (control group, n = 44) or with vitamin D3 supplementation at 400 IU/day (intervention group, n = 43) until 6 months of age. At 6 months, the serum vitamin D (25OHD) of the infants and their mothers, serum bone marker, and infants’ growth parameters were compared between the two groups.

Results

The infants’ serum 25OHD concentration was lower in the control group than intervention group (20.57 ± 12.66 vs. 46.01 ± 16.42 ng/mL, p < 0.01). More infants had vitamin D sufficiency (25OHD of > 20 ng/mL) in the intervention group than control group (93.0% vs. 43.2%, p < 0.01). There were no significant differences in the maternal 25OHD concentrations between the control and intervention groups (25.08 ± 7.75 vs. 23.75 ± 7.64 ng/mL, p = 0.42). Serum calcium, phosphorus, intact parathyroid hormone, alkaline phosphatase, and infants’ growth parameters were comparable between the two groups. After adjustment for the confounding factors, 25OHD concentration in the intervention group was 25.66 ng/mL higher than the control group (95% confidence interval, 19.07–32.25; p < 0.001). Vitamin D supplement contributed to an 88.7% decrease in the prevalence of vitamin D insufficiency/deficiency (relative risk, 0.11; 95% confidence interval, 0.04–0.35; p < 0.01).

Conclusions

Most full-term, exclusively breastfed Thai infants have serum vitamin D concentration below sufficiency level at 6 months of age. However, vitamin D supplementation (400 IU/day) improves their vitamin D status and prevents vitamin D deficiency.

Trial registration

The study was pre-registered in the Thai Clinical Trials Registry (TCTR20190622001) on 22/06/2019.
The effect of intervelar veloplasty under magnification (Sommerlad’s Technique) without tympanostomy on middle ear effusion in cleft palate patients
Authors: Hoghoughi Mohammad Ali , Kazemi Tayebeh , Khojasteh Ali , Habibagahi Raha , Kalkate Zahra , Zarei Zeynab , Hosseinpour Hamidreza , Salimi Maryam
Published: September 2021

Objective

Different surgical techniques and management approaches have been introduced to manage the cleft palate (CP) and its complications, such as otitis media with effusion (OME) and auditory problems. The optimal method, as well as the ideal time for palatoplasty and ventilation tube insertion, are the subject of controversy in the literature. We aimed to evaluate The Effect of Intervelar Veloplasty under Magnification (Sommerlad’s Technique) without Tympanostomy on Middle Ear Effusion in Cleft Palate Patients.

Methods

non-syndromic cleft palate patients from birth to 24 months who needed primary palatoplasty from April 2017 to 2019 were enrolled in this study. intravelar veloplasty (IVVP) surgery under magnification has been done by the same surgeon. Likewise, Otoscopy, Auditory Brainstem Response (ABR), and tympanometry were performed for all the patients before and six months after palatoplasty.

Results

Tympanograms were classified into two categories according to shape and middle ear pressure, and it was done in 42 children (84 ears). Type B curve was seen in 40 cases (80 ears) before surgery which reduced significantly (P < 0.005) to 12 cases in the left ear and 14 cases in the right ear after surgery. So, after surgery, 70 % of the tympanogram of left ears and 66.6 % of the tympanogram of Rt ears were in normal condition (type A tympanometry). ABR was done for 43 patients (86 ears) before surgery and six months after palatoplasty. Data were shown that 40 of the patients had mild to moderate hearing loss before surgery, which reduced significantly (P < 0.005) to 9 in the left ear and 11 in the right ear after palatoplasty. So, after surgery, 79 % of ABR of left ears and 73.8 % of ABR of right ears were in normal status (normal hearing threshold).

Conclusions

Intervelar veloplasty under magnification (Sommerlad’s technique) significantly improved the middle ear effusion without the need for tympanostomy tube insertion.
A review of pears (Pyrus spp.), ancient functional food for modern times
Authors: Hong Sung-Yong , Lansky Ephraim , Kang Sam-Sog , Yang Mihi
Published: September 2021

Background

Pears have been world-widely used as a sweet and nutritious food and a folk medicine for more than two millennia.

Methods

We conducted a review from ancient literatures to current reports to extract evidence-based functions of pears.

Results

We found that pears have many active compounds, e.g., flavonoids, triterpenoids, and phenolic acids including arbutin, chlorogenic acid, malaxinic acid, etc. Most of researchers agree that the beneficial compounds are concentrated in the peels. From various in vitro, in vivo, and human studies, the medicinal functions of pears can be summarized as anti-diabetic,-obese, −hyperlipidemic, −inflammatory, −mutagenic, and -carcinogenic effects, detoxification of xenobiotics, respiratory and cardio-protective effects, and skin whitening effects. Therefore, pears seem to be even effective for prevention from Covid-19 or PM2.5 among high susceptible people with multiple underlying diseases.

Conclusion

For the current or post Covid-19 era, pears have potential for functional food or medicine for both of communicable and non-communicable disease.
Quality improvement in the undergraduate medical curriculum: the need for clinical exposure
Authors: Carter Jemima , Capon Suzanne , Dyer Claire , Whittaker Maya
Published: September 2021

This correspondence article aims to outline the importance of an integrated clinical component within Quality Improvement education in response to the recently published article by Shah et al.. The Quality Improvement and Patient Safety workshops described in the above study were compared with the Quality Improvement module experienced by medical students at King’s College London. The key difference between the two methods of teaching Quality Improvement was the clinical project undertaken by King’s College Students, which helped students gain an appreciation of the pitfalls of instigating change in a clinical environment. The authors feel that this arguably more authentic experience could have benefited the students in the study in making them feel better equipped to use the skills learned in the theoretical workshops in their later careers.
A retrospective study of the impact of health worker strikes on maternal and child health care utilization in western Kenya
Authors: Scanlon Michael L. , Maldonado Lauren Y. , Ikemeri Justus E. , Jumah Anjellah , Anusu Getrude , Bone Jeffrey N. , Chelagat Sheilah , Keter Joann Chebet , Ruhl Laura , Songok Julia , Christoffersen-Deb Astrid
Published: September 2021

Background

There have been dozens of strikes by health workers in Kenya in the past decade, but there are few studies of their impact on maternal and child health services and outcomes. We conducted a retrospective survey study to assess the impact of nationwide strikes by health workers in 2017 on utilization of maternal and child health services in western Kenya.

Methods

We utilized a parent study to enroll women who were pregnant in 2017 when there were prolonged strikes by health workers (“strike group”) and women who were pregnant in 2018 when there were no major strikes (“control group”). Trained research assistants administered a close-ended survey to retrospectively collect demographic and pregnancy-related health utilization and outcomes data. Data were collected between March and July 2019. The primary outcomes of interest were antenatal care (ANC) visits, delivery location, and early child immunizations. Generalized estimating equations were used to estimate risk ratios between the strike and control groups, adjusting for socioeconomic status, health insurance status, and clustering. Adjusted risk ratios (ARR) were calculated with 95% confidence intervals (95%CI).

Results

Of 1341 women recruited in the parent study in 2017 (strike group), we re-consented 843 women (63%) to participate. Of 924 women recruited in the control arm of the parent study in 2018 (control group), we re-consented 728 women (79%). Women in the strike group were 17% less likely to attend at least four ANC visits during their pregnancy (ARR 0.83, 95%CI 0.74, 0.94) and 16% less likely to deliver in a health facility (ARR 0.84, 95%CI 0.76, 0.92) compared to women in the control group. Whether a child received their first oral polio vaccine did not differ significantly between groups, but children of women in the strike group received their vaccine significantly longer after birth (13 days versus 7 days, p = 0.002).

Conclusion

We found that women who were pregnant during nationwide strikes by health workers in 2017 were less likely to receive WHO-recommended maternal child health services. Strategies to maintain these services during strikes are urgently needed.
Interspecies variation of larval locomotion kinematics in the genus Drosophila and its relation to habitat temperature
Authors: Matsuo Yuji , Nose Akinao , Kohsaka Hiroshi
Published: September 2021

Background

Speed and trajectory of locomotion are the characteristic traits of individual species. Locomotion kinematics may have been shaped during evolution towards increased survival in the habitats of each species. Although kinematics of locomotion is thought to be influenced by habitats, the quantitative relation between the kinematics and environmental factors has not been fully revealed. Here, we performed comparative analyses of larval locomotion in 11 Drosophila species.

Results

We found that larval locomotion kinematics are divergent among the species. The diversity is not correlated to the body length but is correlated instead to the habitat temperature of the species. Phylogenetic analyses using Bayesian inference suggest that the evolutionary rate of the kinematics is diverse among phylogenetic tree branches.

Conclusions

The results of this study imply that the kinematics of larval locomotion has diverged in the evolutionary history of the genus Drosophila and evolved under the effects of the ambient temperature of habitats.
Combined homologous recombination repair deficiency and immune activation analysis for predicting intensified responses of anthracycline, cyclophosphamide and taxane chemotherapy in triple-negative breast cancer
Authors: Liao Gaoming , Jiang Zedong , Yang Yiran , Zhang Cong , Jiang Meiting , Zhu Jiali , Xu Liwen , Xie Aimin , Yan Min , Zhang Yunpeng , Xiao Yun , Li Xia
Published: September 2021

Background

Triple-negative breast cancer (TNBC) is a clinically aggressive disease with abundant variants that cause homologous recombination repair deficiency (HRD). Whether TNBC patients with HRD are sensitive to anthracycline, cyclophosphamide and taxane (ACT), and whether the combination of HRD and tumour immunity can improve the recognition of ACT responders are still unknown.

Methods

Data from 83 TNBC patients in The Cancer Genome Atlas (TCGA) was used as a discovery cohort to analyse the association between HRD and ACT chemotherapy benefits. The combined effects of HRD and immune activation on ACT chemotherapy were explored at both the genome and the transcriptome levels. Independent cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) were adopted to validate our findings.

Results

HRD was associated with a longer ACT chemotherapy failure-free interval (FFI) with a hazard ratio of 0.16 (P = 0.004) and improved patient prognosis (P = 0.0063). By analysing both HRD status and ACT response, we identified patients with a distinct TNBC subtype (ACT-S&HR-P) that showed higher tumour lymphocyte infiltration, IFN-γ activity and NK cell levels. Patients with ACT-S&HR-P had significantly elevated immune inhibitor levels and presented immune activation associated with the increased activities of both innate immune cells and adaptive immune cells, which suggested treatment with immune checkpoint blockade as an option for this subtype. Our analysis revealed that the combination of HRD and immune activation enhanced the efficiency of identifying responders to ACT chemotherapy (AUC = 0.91, P = 1.06e−04) and synergistically contributed to the clinical benefits of TNBC patients. A transcriptional HRD signature of ACT response-related prognostic factors was identified and independently validated to be significantly associated with improved survival in the GEO cohort (P = 0.0038) and the METABRIC dataset (P < 0.0001).

Conclusions

These findings highlight that HR deficiency prolongs FFI and predicts intensified responses in TNBC patients by combining HRD and immune activation, which provides a molecular basis for identifying ACT responders.
Novel approach of dermatophytosis eradication in shelters: effect of Pythium oligandrum on Microsporum canis in FIV or FeLV positive cats
Authors: Načeradská Martina , Fridrichová Michaela , Kolářová Martina Frühauf , Krejčová Tereza
Published: September 2021

Background

Shelters and similar facilities with a high concentration and fluctuation of animals often have problems with various infections, which are usually difficult to solve in such environments and are very expensive to treat. This study investigated the eradication ofMicrosporum canis, the widespread cause of zoonotic dermatophytosis in shelters, even in immunosuppressed feline leukaemia virus or feline immunodeficiency virus positive cats.

Results

Our study showed the increased effectiveness of an alternative topical therapy for affected animals using the mycoparasitic fungusPythium oligandrum, which is gentler and cheaper than the standard systemic treatment with itraconazole, and which can also be easily used as a preventative treatment. A decrease in the number ofM. caniscolonies was observed in cats treated with a preparation containingP. oligandrum2 weeks after the start of therapy (2 cats with P-1 score, 2 cats with P-2 score, 5 cats with P-3 score) compared with the beginning of the study (9 cats with P-3 score = massive infection). The alternative topical therapy with a preparation containingP. oligandrumwas significantly more effective compared with the commonly used systemic treatment using itraconazole 5 mg/kg in a 6-week pulse. After 16 weeks of application of the alternative topical therapy, the clinical signs of dermatophytosis were eliminated throughout the whole shelter.

Conclusion

The complete elimination of the clinical signs of dermatophytosis in all cats indicates that this therapy will be useful for the management and prevention of zoonotic dermatophytosis in animal shelters.
Does low income effects 5-year mortality of hepatocellular carcinoma patients?
Authors: Kim Dong Jun , Yoo Ji Won , Chang Jong Wha , Yamashita Takashi , Park Eun-Cheol , Han Kyu-Tae , Kim Seung Ju , Kim Sun Jung
Published: September 2021

Background

In Korea, the universal health system offers coverage to all members of society. Despite this, it is unclear whether risk of death from hepatocellular carcinoma (HCC) varies depending on income. We evaluated the impact of low income on HCC mortality.

Methods

The Korean National Health Insurance sampling cohort was used to identify new HCC cases (n = 7325) diagnosed between 2004 and 2008, and the Korean Community Health Survey data were used to investigate community-level effects. The main outcome was 5-year all-cause mortality risk, and Cox proportional hazard models were applied to investigate the individual- and community-level factors associated with the survival probability of HCC patients.

Results

From 2004 to 2008, there were 4658 new HCC cases among males and 2667 new cases among females. The 5-year survival proportion of males was 68%, and the incidence per person-year was 0.768; the female survival proportion was 78%, and the incidence per person-year was 0.819. Lower income was associated with higher hazard ratio (HR), and HCC patients with hepatitis B (HBV), alcoholic liver cirrhosis, and other types of liver cirrhosis had higher HRs than those without these conditions. Subgroup analyses showed that middle-aged men were most vulnerable to the effects of low income on 5-year mortality, and community-level characteristics were associated with survival of HCC patients.

Conclusion

Having a low income significantly affected the overall 5-year mortality of Korean adults who were newly diagnosed with HCC from 2004 to 2008. Middle-aged men were the most vulnerable. We believe our findings will be useful to healthcare policymakers in Korea as well as to healthcare leaders in countries with NHI programs who need to make important decisions about allocation of limited healthcare resources according to a consensually accepted and rational framework.
Revisit the practice of lymph node biopsy in patients diagnosed as ductal carcinoma in situ before operation: a retrospective analysis of 682 cases and evaluation of the role of breast MRI
Authors: Lai Hung-Wen , Chang Yi-Lin , Chen Shou-Tung , Chang Yu-Jun , Wu Wen-Pei , Chen Dar-Ren , Kuo Shou-Jen , Liao Chiung-Ying , Wu Hwa-Koon
Published: September 2021

Background

The optimal axillary lymph node (ALN) management strategy in patients diagnosed with ductal carcinoma in situ (DCIS) preoperatively remains controversial. The value of breast magnetic resonance imaging (MRI) to predict ALN metastasis pre-operative DCIS patients was evaluated.

Methods

Patients with primary DCIS with or without pre-operative breast MRI evaluation and underwent breast surgery were recruited from single institution. The value of breast MRI for ALN evaluation, predictors of breast and ALN surgeries, upgrade from DCIS to invasive cancer, and ALN metastasis were analyzed.

Results

A total of 682 cases with pre-operative diagnosis of DCIS were enrolled in current study. The rate of upgrade to invasive cancer were found in 34.2% of specimen, and this upgrade rate is 23% for patients who received breast conserving surgery and 40.7% for mastectomy (p < 0.01). Large pre-operative imaging tumor size and post-operative invasive component were risk factors to ALN metastasis. Breast MRI had 53.8% sensitivity, 77.8% specificity, 14.9% positive predictive value, 95.9% negative predictive value (NPV), and 76.2% accuracy to predict ALN metastasis in pre-OP DCIS patients. In MRI node-negative breast cancer patients with MRI tumor size < 3 cm, the NPV was 96.4%, and all these false-negative cases were N1. Pre-OP diagnosed DCIS patients with MRI tumor size < 3 cm and node negative suitable for BCS could safely omit SLNB if whole breast radiotherapy is to be performed.

Conclusion

Breast MRI had high NPV to predict ALN metastasis in pre-OP DCIS patients, which is useful and could be provided as shared decision-making reference.
Characterization and purification of Algerian natural bentonite for pharmaceutical and cosmetic applications
Authors: Babahoum Nabil , Ould Hamou Malek
Published: September 2021

Introduction

Bentonitic clays from the Hammam Boughrara deposit in the Maghnia area (northwestern Algeria) were studied by mineralogical, chemical and physicochemical characterization to evaluate their potential suitability as raw and purified materials in pharmaceutical and cosmetic applications.

Methodology

Natural bentonite was purified by Na+ ion exchange treatment combined with sedimentation techniques. Before use in the pharmaceutical industry, bentonite samples must be safe and conform to recommendations and directives of pharmacopeia. A set of technological tests were investigated with the samples, such as cation exchange capacity (CEC), specific surface area (SSA), swelling capacity (SC),sedimentation volume (SV) and viscosity, and mineralogical, chemical and microbial properties were also identified by X-ray fluorescence (XRF), X-ray diffraction (XRD) and scanning electron microscopy (SEM).

Results

Mineralogical data proved that the raw bentonite is mainly composed of smectite and illite with small quantities of gangue minerals such quartz, feldspars (orthoclase and albite) and calcite. The purified bentonite matches the mineralogical properties of Wyoming bentonite as an international standard clay (deposits of high economic value). Quartz and feldspars were successfully eliminated in the absence of illite and calcite after beneficiation. Investigation of chemical analyses indicated that the contents of trace elements (particularly Pb and As) were below the more restrictive limits proposed by major pharmacopeias for raw and purified bentonite clay. For microbiological tests, the absence of Escherichia coli, Salmonella species, Staphylococcus aureus and Pseudomonas aeruginosa was confirmed. Moreover, we note that a high cation exchange capacity, large surface area, and good swelling capacity and sedimentation volume were also obtained for purified bentonite.

Conclusion

In view of the fundamentals of major pharmacopoeias for the use of bentonite in pharmacies and considering the results obtained, we identified a pharmaceutically acceptable designation for purified Algerian bentonite, which can be used as a pharmaceutical excipient and in cosmetic products such as creams, powders and emulsions.
Distinct transcriptional programs stratify ovarian cancer cell lines into the five major histological subtypes
Authors: Barnes Bethany M. , Nelson Louisa , Tighe Anthony , Burghel George J. , Lin I-Hsuan , Desai Sudha , McGrail Joanne C. , Morgan Robert D. , Taylor Stephen S.
Published: September 2021

Background

Epithelial ovarian cancer (OC) is a heterogenous disease consisting of five major histologically distinct subtypes: high-grade serous (HGSOC), low-grade serous (LGSOC), endometrioid (ENOC), clear cell (CCOC) and mucinous (MOC). Although HGSOC is the most prevalent subtype, representing 70–80% of cases, a 2013 landmark study by Domcke et al. found that the most frequently used OC cell lines are not molecularly representative of this subtype. This raises the question, if not HGSOC, from which subtype do these cell lines derive? Indeed, non-HGSOC subtypes often respond poorly to chemotherapy; therefore, representative models are imperative for developing new targeted therapeutics.

Methods

Non-negative matrix factorisation (NMF) was applied to transcriptomic data from 44 OC cell lines in the Cancer Cell Line Encyclopedia, assessing the quality of clustering into 2–10 groups. Epithelial OC subtypes were assigned to cell lines optimally clustered into five transcriptionally distinct classes, confirmed by integration with subtype-specific mutations. A transcriptional subtype classifier was then developed by trialling three machine learning algorithms using subtype-specific metagenes defined by NMF. The ability of classifiers to predict subtype was tested using RNA sequencing of a living biobank of patient-derived OC models.

Results

Application of NMF optimally clustered the 44 cell lines into five transcriptionally distinct groups. Close inspection of orthogonal datasets revealed this five-cluster delineation corresponds to the five major OC subtypes. This NMF-based classification validates the Domcke et al. analysis, in identifying lines most representative of HGSOC, and additionally identifies models representing the four other subtypes. However, NMF of the cell lines into two clusters did not align with the dualistic model of OC and suggests this classification is an oversimplification. Subtype designation of patient-derived models by a random forest transcriptional classifier aligned with prior diagnosis in 76% of unambiguous cases. In cases where there was disagreement, this often indicated potential alternative diagnosis, supported by a review of histological, molecular and clinical features.

Conclusions

This robust classification informs the selection of the most appropriate models for all five histotypes. Following further refinement on larger training cohorts, the transcriptional classification may represent a useful tool to support the classification of new model systems of OC subtypes.
Factors associated with medical complications after body art among Israeli adults: a retrospective study
Authors: Korn Liat , Bonny-Noach Hagit , Koren Gideon , Nissanholtz-Gannot Rachel
Published: September 2021

Introduction

Body-art, including tattoos and piercings, is steadily increasing world-wide but with relatively limited reporting of adverse outcomes. The objective of the present study was to identify correlates that would facilitate a preventative strategy to minimize adverse effects of body-art.

Methods

We examined patterns of body-art, health risk and perceptions among 921 participants (54% female, mean age of 35; SD = 10.8) through in-person questionnaire.

Results

A significantly lower frequency of those with body-art acknowledged that not all venues (parlors, clinics, etc.) are safe in terms of health and hygiene (84.7%t vs. 96.6%, p < .001) as compared to those without body-art. Similarly, knowledge of the need for a Ministry of Health certification was reported with lower frequency (77.2% vs. 94.5%, p < .001) among those with body-art. Those who experienced medical complications reported higher frequencies of smoking cigarettes and hookah as well as using ecstasy (MDMA). The risk of medical complication after body-art was 4 times higher in those who used ecstasy (OR = 3.97; CI 1.0–14.4; p < 0.05). In addition, it was more than 3 times higher for street or home tattooing as compared to studio or a licensed medical center (OR = 3.59; CI 1.32–9.76; p < .01), as well as almost 3 times higher among those who did not receive information before performing body-art (OR = 2.70; CI 1.05–6.92; p < .05) and who had somebody other than themselves decide on the body-art design (OR = 2.68; CI 1.00–7.19; p < .05).

Conclusions

A targeted informational-preventative program should be developed, informed by the risks highlighted in this study. In addition, it would be necessary to draft policies related to regulation and enforcement in order to more effectively manage body-art service provision. The Ministry of Health should supervise and guide tattooists and practitioners regarding the health risks of body-art and offer training and raise awareness among potential clients.
Valproic acid autoinduction: a case-based review
Authors: Bennett Sean , Shad Mujeeb U.
Published: September 2021

Although valproic acid (VPA) induces the metabolism of multiple other drugs, the clinical reports of VPA autoinduction are rare. A comprehensive literature search yielded only one published case series, which provided the rationale to conduct a review of the published cases along with a new case of VPA autoinduction. Although there may be myriad of reasons for lack of published cases of VPA autoinduction, potential underreporting may be one of the core reasons. Lack of understanding into the highly complex metabolism of VPA may also make it difficult to recognize and report VPA autoinduction. However, it is important to mention that in addition to autoinduction increased elimination of VPA may be mediated by several pharmacokinetic (PK) factors, such as drug interactions, genetic polymorphisms of metabolic enzymes, and protein displacement reactions. As VPA is metabolized by multiple metabolic pathways, the risk for drug interactions is relatively high. There is also a growing evidence for high genetic inducibility of some enzymes involved in VPA metabolism. Protein displacement reactions with VPA increase the biologically active and readily metabolizable free fraction and pose a diagnostic challenge as they are usually not requested by most clinicians. Thus, monitoring of free fraction with total VPA levels may prevent clinically serious outcomes and optimize VPA treatment in clinically challenging patients. This case-based review compares the clinical data from three published cases and a new case of VPA autoinduction to enhance clinicians' awareness of this relatively rare but clinically relevant phenomenon along with a discussion of potential underlying mechanisms.
Exploring tertiary EFL practitioners’ knowledge base component of assessment literacy: implications for teacher professional development
Authors: Latif Muhammad Wasim
Published: September 2021

Language teachers’ assessment literacy has been a much debated subject in the educational arena recently. Teachers’ assessment knowledge base and skills, important aspects of their assessment literacy, have been extensively investigated at the school level; however, the research on this subject in the tertiary EFL context remains underdeveloped. This study reports findings of tertiary EFL teachers’ assessment literacy in terms of their assessment knowledge base in the context of Saudi Arabia. The study is informed by sociocultural theoretical background, with pragmatism as the philosophical underpinning. It uses an adapted instrument called Classroom Assessment Literacy Questionnaire, and the data are obtained from 80 questionnaire respondents. The statistical analysis of the data revealed that tertiary EFL teachers’ current assessment knowledge base is very limited and not consistent with the contemporary trends and approaches to educational assessment in terms of their preparation and readiness for the continuously mounting challenges posed by classroom-based assessments. These results indicating gaps and inadequacies in tertiary EFL practitioners’ assessment literacy have strong implications for teacher development in the area of assessment and testing at the level of policy, practice and professional development programmes.
A facile synthesis of GO/CuO-blended nanofiber sensor electrode for efficient enzyme-free amperometric determination of glucose
Authors: Gijare Medha , Chaudhari Sharmila , Ekar Satish , Garje Anil
Published: September 2021

The development of biosensors with innovative nanomaterials is crucial to enhance the sensing performance of as-prepared biosensors. In the present research work, we prepared copper (II) oxide (CuO) and graphene oxide (GO) composite nanofibers using the hydrothermal synthesis route. The structural and morphological properties of as-prepared GO/CuO nanofibers were analyzed using an X-ray diffractometer, field-emission scanning, energy dispersive X-ray analysis, Fourier transmission infrared spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. The results indicated GO/CuO nanofibers exhibit nanosized diameters and lengths in the order of micrometers. These GO/CuO nanofibers were employed to prepare non-enzymatic biosensors (GO/CuO nanofibers/FTO (fluorine-doped tin oxide)) modified electrodes for enhanced glucose detection. The sensing performance of the biosensors was evaluated using linear sweep voltammetry (LSV) and chronoamperometry in phosphate buffer solution (PBS). GO/CuO/FTO biosensor achieved high sensitivity of 1274.8 μA mM−1cm−2having a linear detection range from 0.1 to 10 mM with the lower detection limit (0.13 μM). Further, the prepared biosensor showed good reproducibility repeatability, excellent selectivity, and long-time stability. Moreover, the technique used for the preparation of the GO/CuO composite is simple, rapid, cost-effective, and eco-friendly. These electrodes are employed for the detection of glucose in blood serum with RSD ~ 1.58%.
Structural characteristics of the bone surrounding dental implants placed into the tail-suspended mice
Authors: Otsu Yuto , Matsunaga Satoru , Furukawa Takehiro , Kitamura Kei , Kasahara Masaaki , Abe Shinichi , Nakano Takayoshi , Ishimoto Takuya , Yajima Yasutomo
Published: September 2021

Background

There are many unclear points regarding local structural characteristics of the bone surrounding the implant reflecting the mechanical environment.

Purpose

The purpose of this study is to quantitatively evaluate bone quality surrounding implants placed into the femurs of mice in an unloading model, and to determine the influence of the mechanical environment on bone quality.

Methods

Twenty 12-week-old male C57BL6/NcL mice (n = 5/group) were used as experimental animals. The mice were divided into two groups: the experimental group (n = 10) which were reared by tail suspension, and the control group (n = 10) which were reared normally. An implant was placed into the femur of a tail-suspended mouse, and after the healing period, they were sacrificed and the femur was removed. After micro-CT imaging, Villanueva osteochrome bone stain was performed. It was embedded in unsaturated polyester resin. The polymerized block was sliced passing through the center of the implant body. Next, 100-μm-thick polished specimens were prepared with water-resistant abrasive paper. In addition to histological observation, morphometric evaluation of cancellous bone was performed, and the anisotropy of collagen fibers and biological apatite (BAp) crystals was analyzed.

Results

As a result, the femoral cortical bone thickness and new peri-implant bone mass showed low values in the tail suspension group. The uniaxial preferential orientation of BAp c-axis in the femoral long axis direction in the non-implant groups, but biaxial preferential orientation of BAp c-axis along the long axis of implant and femoral long axis direction were confirmed in new bone reconstructed by implant placement. Collagen fiber running anisotropy and orientation of BAp c-axis in the bone surrounding the implant were not significantly different due to tail suspension.

Conclusions

From the above results, it was clarified that bone formation occurs surrounding the implant even under extremely low load conditions, and bone microstructure and bone quality adapted to the new mechanical environment are acquired.
A meta-analysis of observational studies on anticholinergic burden and fracture risk: evaluation of conventional burden scales
Authors: Ogawa Yukari , Hirai Toshinori , Mihara Kiyoshi
Published: September 2021

Background

Anticholinergic burden potentially increases the risk of fracture. Although there are various anticholinergic burden scales, little is known about the inter-scale compatibility regarding the relationship of anticholinergic burden with fracture risk. We performed meta-analysis to examine the association of fracture risk with anticholinergic burden measured using various scales.

Methods

Primary literature was retrieved from PubMed (1966 to March, 2021), the Cochrane Library (1974 to March, 2021), Scopus (1970 to March, 2021), and Ichushi-web (1983 to March, 2021). Cohort and case-control studies that evaluated the association between any fracture and anticholinergic drugs were included. Additionally, we included studies in which patients were administered anticholinergic drugs included on the anticholinergic risk scale (ARS), anticholinergic cognitive burden (ACB), anticholinergic drug scale, or drug burden index-anticholinergic component. Random effects models were used to calculate pooled relative risk (RR) and 95% confidence interval (CI) due to heterogeneity among the studies. Publication bias was examined by funnel plots and the Begg’s test.

Results

A total of 49 datasets from 10 studies were included in the meta-analysis. Six of the 10 studies included only patients aged over 65 years, who accounted for 93% of the total study population (453,186/487,247). Meta-analysis indicated a positive relationship between use of anticholinergic drugs and fracture risk, regardless of the anticholinergic burden scale used. However, the relationship between anticholinergic burden and fracture risk varied depending on the scale used. Fracture risk increased linearly with increasing anticholinergic burden measured using ARS. ARS 1 point was associated with 28% increase in fracture risk, ARS 1–2 point(s) with 39%, ARS 2 points with 54%, ARS 3 points with 66%, and ARS ≥ 4 points with 77%. On the other hand, ACB 1 point and ACB 2 points were associated with similar fracture risk (pooled RR [95% CI]: overall; 1.28 [1.18–1.39], 1 point; 1.12 [1.06–1.18], 2 points; 1.15 [1.08–1.23]).

Conclusions

This result suggests that the relationship between anticholinergic drug burden and fracture risk may differ depending on the anticholinergic burden scale used.