bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of active learning and online discussions on the academic performances of dental students
Authors: Lim Jaeseo , Ko Hyunwoong , Park Jooyong , Ihm Jungjoon
Published: April 2022

Background

COVID-19 caused significant confusion around the world, and dental education was no exception. Therefore, in line with the demands of the times, this study sought to determine the applicability of online active learning to dental education.

Methods

This study was conducted in the second semester of 2020 at a school of dentistry in a selective university in Korea. A total of 114 dental students were recruited. Participants were assigned to four different groups (lecture and discussion [LD], lecture and discussion with instructor’s worksheet [LW], self-study and discussion [SSD], and self-study and discussion with instructor’s worksheet [SW]) using the random breakout room function in the Zoom video conference application. Their final test scores were then analyzed using analysis of variance and the online active learning results were compared with the offline learning results.

Results

The scores were highest for the transfer type items in the SSD group, followed by the SW group and the two lecture groups, which had no significant differences. These scores and pattern differences between the groups were similar for all items. The results suggested that studying by oneself rather than simply listening to lectures enhanced the effects of the discussions and led to higher learning outcomes. In addition, the effect of the instructor's intervention in the middle of the discussion varied depending on the pre-learning activities of discussion. As with previous offline experiments, self-study followed by group discussion had higher learning outcomes for both the verbatim and transfer type items.

Conclusions

In agreement with the Interactive, Constructive, Active, and Passive (ICAP) framework and other active learning theories, the findings clearly indicated that online active learning was applicable to dental students, and when self-study precedes discussion, the learning is richer and the learning outcomes are better.
Engineered Cas12a-Plus nuclease enables gene editing with enhanced activity and specificity
Authors: Huang Hongxin , Huang Guanjie , Tan Zhihong , Hu Yongfei , Shan Lin , Zhou Jiajian , Zhang Xin , Ma Shufeng , Lv Weiqi , Huang Tao , Liu Yuchen , Wang Dong , Zhao Xiaoyang , Lin Ying , Rong Zhili
Published: April 2022

Background

The CRISPR-Cas12a (formerly Cpf1) system is a versatile gene-editing tool with properties distinct from the broadly used Cas9 system. Features such as recognition of T-rich protospacer-adjacent motif (PAM) and generation of sticky breaks, as well as amenability for multiplex editing in a single crRNA and lower off-target nuclease activity, broaden the targeting scope of available tools and enable more accurate genome editing. However, the widespread use of the nuclease for gene editing, especially in clinical applications, is hindered by insufficient activity and specificity despite previous efforts to improve the system. Currently reported Cas12a variants achieve high activity with a compromise of specificity. Here, we used structure-guided protein engineering to improve both editing efficiency and targeting accuracy of Acidaminococcus sp. Cas12a (AsCas12a) and Lachnospiraceae bacterium Cas12a (LbCas12a).

Results

We created new AsCas12a variant termed “AsCas12a-Plus” with increased activity (1.5~2.0-fold improvement) and specificity (reducing off-targets from 29 to 23 and specificity index increased from 92% to 94% with 33 sgRNAs), and this property was retained in multiplex editing and transcriptional activation. When used to disrupt the oncogenic BRAFV600E mutant, AsCas12a-Plus showed less off-target activity while maintaining comparable editing efficiency and BRAFV600E cancer cell killing. By introducing the corresponding substitutions into LbCas12a, we also generated LbCas12a-Plus (activity improved ~1.1-fold and off-targets decreased from 20 to 12 while specificity index increased from 78% to 89% with 15 sgRNAs), suggesting this strategy may be generally applicable across Cas12a orthologs. We compared Cas12a-Plus, other variants described in this study, and the reported enCas12a-HF, enCas12a, and Cas12a-ultra, and found that Cas12a-Plus outperformed other variants with a good balance for enhanced activity and improved specificity.

Conclusions

Our discoveries provide alternative AsCas12a and LbCas12a variants with high specificity and activity, which expand the gene-editing toolbox and can be more suitable for clinical applications.
Time spent in outdoor light is associated with the risk of dementia: a prospective cohort study of 362094 participants
Authors: Ma Ling-Zhi , Ma Ya-Hui , Ou Ya-Nan , Chen Shi-Dong , Yang Liu , Dong Qiang , Cheng Wei , Tan Lan , Yu Jin-Tai
Published: April 2022

Background

Data on the association between free-living daytime sunlight exposure and incident dementia are scarce. The objective is to evaluate whether the time spent in outdoor light is related to the dementia risk and to investigate whether the optimal duration varies with clinical parameters.

Methods

Data were from a prospective cohort of 362,094 UK Biobank participants. A questionnaire survey was conducted to investigate how many hours the participants spent outdoors on typical summer and winter days. A restricted cubic spline (RCS) was performed to explore the potential nonlinear relationship between sunlight exposure and the risk of dementia. We used multivariate Cox proportional hazard regression models to estimate the hazard ratios (HRs) for the associations between sunlight exposure and dementia outcomes, with the change points as a reference.

Results

After a median follow-up of 9.0 years, 4149 (1.15%) individuals were diagnosed with dementia. RCS showed a J-shaped relationship between time spent in outdoor light and the dementia risk, with the lowest risk at three change points (1.5 h/day on average, 2 h/day in summer, and 1 h/day in winter). Cox hazard regression models showed a marked increase in risk at low exposure (HR=1.287, 95%CI 1.094–1.515) but a relatively slow increase at higher exposure (HR=1.070, 95%CI 1.031–1.10). Results are more pronounced among participants over 60 years old, females, and those with exactly 7 h of sleep every night.

Conclusions

Sunlight exposure had a J-shaped association with dementia risk. Giving detailed guidance on sunlight exposure can effectively prevent dementia.
Clinically actionable cancer somatic variants (CACSV): a tumor interpreted dataset for analytical workflows
Authors: Sobahy Turki M. , Tashkandi Ghassan , Bahussain Donya , Al-Harbi Raneem
Published: April 2022

Background

The recent development and enormous application of parallel sequencing technology in oncology has produced immense amounts of cell-specific genetic information. However, publicly available cell-specific genetic variants are not explained by well-established guidelines. Additionally, cell-specific variants interpretation and classification has remained a challenging task and lacks standardization. The Association for Molecular Pathology (AMP), the American Society of Clinical Oncology (ASCO), and the College of American Pathologists (CAP) published the first consensus guidelines for cell-specific variants cataloging and clinical annotations.

Methods

AMP–ASCO–CAP recommended sources and information were downloaded and used as follows: relative knowledge in oncology clinical practice guidelines; approved, investigative or preclinical drugs; supporting literature and each gene-tumor site correlation. All information was homogenized into a single knowledgebase. Finally, we incorporated the consensus recommendations into a new computational method.

Results

A subset of cancer genetic variants was manually curated to benchmark our method and well-known computational algorithms. We applied the new method on freely available tumor-specific databases to produce a clinically actionable cancer somatic variants (CACSV) dataset in an easy-to-integrate format for most clinical analytical workflows. The research also showed the current challenges and limitations of using different classification systems or computational methods.

Conclusion

CACSV is a step toward cell-specific genetic variants standardized interpretation as it is readily adaptable by most clinical laboratory pipelines for somatic variants clinical annotations. CACSV is freely accessible at (https://github.com/tsobahytm/CACSV/tree/main/dataset).
Angiopoietin2-mediated caveolin1 phosphorylation regulating transcytosis of renal tubular epithelial cell contributes to the occurrence of albuminuria under high glucose exposure
Authors: Liu Jing , Yao Junxia , Zhao Yi , Su Jinxuan , Ye Jiajia , Wang Yumei
Published: April 2022

Background

Microlbuminuria is the earliest clinical evidence of diabetic kidney disease (DKD) and contributes to the induction and/or progression of DKD. Previous studies have shown that increased expression of angiopoietin2 (ANGPT2) is correlated with an increase in albuminuria. However, the critical role of ANGPT2 in albuminuria development remains unclear. Some studies have shown the significance of transcytosis in the occurrence of albuminuria, but it is unknown whether it takes place in albumin recycling in renal tubular cells of patients with DKD. Furthermore, the potential mechanism of this association also remains unclear.

Methods

In this study, human renal tubular epithelial cells (HK-2) were cultured with high glucose in a Transwell plate to establish a transcytosis model, while C57BL/6 mice were intraperitoneally injected with streptozotocin to establish a DKD model. The expression of ANGPT2 and caveolin1 (CAV1) phosphorylation was dectected through immunohistochemistry and western blot analysis.

Results

Transcytosis of albumin in renal tubular epithelial cells was downregulated after high glucose exposure, and increased expression of ANGPT2 and CAV1 phosphorylation both in vivo and in vitro was observed. Inhibition of ANGPT2 and CAV1 independently promoted transcytosis. Furthermore, ANGPT2 downregulation inhibited CAV1 phosphorylation, whereas CAV1 phosphorylation had no effect on the expression of ANGPT2.

Conclusions

ANGPT2 reduces albumin transcytosis across renal tubular epithelial cells under high glucose conditions by activating CAV1 phosphorylation, thus increasing albuminuria in DKD. These findings suggested that ANGPT2 and CAV1 may be promising therapeutic targets for albuminuria in DKD.
Timing of pharmacologic venous thromboembolism prophylaxis initiation for trauma patients with nonoperatively managed blunt abdominal solid organ injury: a systematic review and meta-analysis
Authors: Lamb Tyler , Lenet Tori , Zahrai Amin , Shaw Joseph R. , McLarty Ryan , Shorr Risa , Le Gal Grégoire , Glen Peter
Published: April 2022

Background

Blunt abdominal solid organ injury is common and is often managed nonoperatively. Clinicians must balance risk of both hemorrhage and thrombosis. The optimal timing of pharmacologic venous thromboembolism prophylaxis (VTEp) initiation in this population is unclear. The objective was to evaluate early (< 48 h) compared to late initiation of VTEp in adult trauma patients with blunt abdominal solid organ injury managed nonoperatively.

Methods

Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched from inception to March 2021. Studies comparing timeframes of VTEp initiation were considered. The primary outcome was failure of nonoperative management (NOM) after VTEp initiation. Secondary outcomes included risk of transfusion, other bleeding complications, risk of deep vein thrombosis (DVT) and pulmonary embolism, and mortality.

Results

Ten cohort studies met inclusion criteria, with a total of 4642 patients. Meta-analysis revealed a statistically significant increase in the risk of failure of NOM among patients receiving early VTEp (OR 1.76, 95% CI 1.01–3.05,p = 0.05). There was no significant difference in risk of transfusion. Odds of DVT were significantly lower in the early group (OR 0.36, 95% CI 0.22–0.59,p < 0.0001). There was no difference in mortality (OR 1.50, 95% CI 0.82–2.75,p = 0.19). All studies were at serious risk of bias due to confounding.

Conclusions

Initiation of VTEp earlier than 48 h following hospitalization is associated with an increased risk of failure of NOM but a decreased risk of DVT. Absolute failure rates of NOM are low. Initiation of VTEp at 48 h may balance the risks of bleeding and VTE.
Squamous cell carcinoma of the lung presenting as a fungating ulcerated skin lesion: a case report
Authors: Chisenga Rose , Adenwala Tasneem , Kim William , Mujuni Daniel , Samuel Rachel
Published: April 2022

Background

Our patient presents with a novel presentation of a fungated ulcerated skin lesion as the initial presentation of lung cancer. The literature describes skin metastases from lung cancer as nodular, papular, and zosteriform. Our case is a fungating ulcerated skin lesion which is not widely reported in literature. There is a still a need for more data on the clinical presentation and prognosis of such cases as it will elucidate the diagnostic challenges and treatment management.

Case presentation

We present a case of a 55 year old Caucasian male with a 60-pack-year smoking history initially presenting with a nodule on his right upper back that quickly fungated and ulcerated requiring surgical excision. Biopsy of both the skin lesion and the lung mass confirmed squamous cell carcinoma (SCC) and the lung mass being the primary tumor. The patient’s clinical and functional status severely declined during his hospital stay and was later discharged to hospice without therapeutic intervention. He later expired a month after hospice stay.

Conclusions

Although uncommon, this case clearly illustrates that skin metastases can be the initial finding of primary lung cancer and that not all patients with lung cancer will present with bronchopulmonary symptoms. It also illustrates that a fungating ulcerated lesion can be the initial presentation of lung cancer in addition to nodular, papular, and zosteriform presentations noted in the literature.
Global status of antimicrobial resistance among environmental isolates of Vibrio cholerae O1/O139: a systematic review and meta-analysis
Authors: Yuan Xin-hui , Li Yu-mei , Vaziri Ali Zaman , Kaviar Vahab Hassan , Jin Yang , Jin Yu , Maleki Abbas , Omidi Nazanin , Kouhsari Ebrahim
Published: April 2022

Background

Vibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment failures.

Objective

This meta-analysis aimed to evaluate the weighted pooled resistance (WPR) rates in V. cholerae O1/O139 isolates obtained from environmental samples.

Methods

We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Subgroup analyses were then employed by publication year, geographic areas, and the quality of studies. Statistical analyses were conducted using STATA software (ver. 14.0).

Results

A total of 20 studies investigating 648 environmental V. cholerae O1/O139 isolates were analysed. The majority of the studies were originated from Asia (n = 9). In addition, a large number of studies (n = 15 i.e. 71.4%) included in the meta-analysis revealed the resistance to cotrimoxazole and ciprofloxacin. The WPR rates were as follows: cotrimoxazole 59%, erythromycin 28%, tetracycline 14%, doxycycline 5%, and ciprofloxacin 0%. There was increased resistance to nalidixic acid, cotrimoxazole, furazolidone, and tetracycline while a decreased resistance to amoxicillin, ciprofloxacin, erythromycin, chloramphenicol, ampicillin, streptomycin, and ceftriaxone was observed during the years 2000–2020. A significant decrease in the doxycycline and ciprofloxacin-resistance rates in V. cholerae O1/O139 isolates was reported over the years 2011–2020 which represents a decrease in 2001–2010 (p < 0.05).

Conclusions

Fluoroquinolones, gentamicin, ceftriaxone, doxycycline, kanamycin, and cefotaxime showed the highest effectiveness and the lowest resistance rate. However, the main interest is the rise of antimicrobial resistance in V. cholerae strains especially in low-income countries or endemic areas, and therefore, continuous surveillance, careful appropriate AST, and limitation on improper antibiotic usage are crucial.
Viral haemorrhagic fevers and malaria co-infections among febrile patients seeking health care in Tanzania
Authors: Rugarabamu Sima , Rumisha Susan F. , Mwanyika Gaspary O. , Sindato Calvin , Lim Hee-Young , Misinzo Gerald , Mboera Leonard E. G.
Published: April 2022

Background

In recent years there have been reports of viral haemorrhagic fever (VHF) epidemics in sub-Saharan Africa where malaria is endemic. VHF and malaria have overlapping clinical presentations making differential diagnosis a challenge. The objective of this study was to determine the prevalence of selected zoonotic VHFs and malaria co-infections among febrile patients seeking health care in Tanzania.

Methods

This facility-based cross-sectional study was carried out between June and November 2018 in Buhigwe, Kalambo, Kyela, Kilindi, Kinondoni, Kondoa, Mvomero, and Ukerewe districts in Tanzania. The study involved febrile patients seeking health care from primary healthcare facilities. Blood samples were collected and tested for infections due to malaria, Crimean-Congo haemorrhagic fever (CCHF), Ebola virus disease (EVD), Marburg virus disease (MVD), Rift Valley fever (RVF) and yellow fever (YF). Malaria infections were tested using rapid diagnostics tests while exposure to VHFs was determined by screening for immunoglobulin M antibodies using commercial enzyme-linked immunosorbent assays. The Chi-square test was used to compare the proportions.

Results

A total of 308 participants (mean age = 35 ± 19 years) were involved in the study. Of these, 54 (17.5%) had malaria infection and 15 (4.8%) were positive for IgM antibodies against VHFs (RVF = 8; CCHF = 2; EBV = 3; MBV = 1; YF = 1). Six (1.9%) individuals had both VHF (RVF = 2; CCHF = 1; EVD = 2; MVD = 1) and malaria infections. The highest co-infection prevalence (0.6%) was observed among individuals aged 46‒60 years (P < 0.05). District was significantly associated with co-infection (P < 0.05) with the highest prevalence recorded in Buhigwe (1.2%) followed by Kinondoni (0.9%) districts. Headache (100%) and muscle, bone, back and joint pains (83.3%) were the most significant complaints among those infected with both VHFs and malaria (P = 0.001).

Conclusions

Co-infections of VHF and malaria are prevalent in Tanzania and affect more the older than the younger population. Since the overlapping symptoms in co-infected individuals may challenge accurate diagnosis, adequate laboratory diagnosis should be emphasized in the management of febrile illnesses.
Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China–Myanmar border during 2008‒2017
Authors: Wang Zhensheng , Wei Chunyan , Pan Yunchun , Wang Zhihua , Ji Xin , Chen Qianqian , Zhang Lianhui , Wang Zenglei , Wang Heng
Published: April 2022

Background

Plasmodium vivax remains the predominant species at the China–Myanmar border, imposing a major challenge to the recent gains in regional malaria elimination. To closely supervise the emerging of drug resistance in this area, we surveyed the variations in genes potentially correlated with drug resistance in P. vivax parasite and the possible drug selection with time.

Methods

A total of 235 P. vivax samples were collected from patients suffering uncomplicated malaria at Yingjiang, Tengchong, and Longling counties, and Nabang port in China, Yunnan province, and Laiza sub-township in Myanmar, from 2008 to 2017. Five potential drug resistance genes were amplified utilizing nested-PCR and analyzed, including pvdhfr, pvdhps, pvmdr1, pvcrt-o, and pvk12. The Pearson’s Chi-squared test or Fisher’s exact test were applied to determine the statistical frequency differences of mutations between categorical data.

Results

The pvdhfr F57I/L, S58R, T61M and S117T/N presented in 40.6%, 56.7%, 40.1%, and 56.0% of the sequenced P. vivax isolates, and these mutations significantly decreased with years. The haplotype formed by these quadruple mutations predominated in Yingjiang, Tengchong, Longling and Nabang. While a mutation H99S/R (56.6%) dominated in Laiza and increased with time. In pvdhps, the A383G prevailed in 69.2% of the samples, which remained the most prevalent haplotype. However, a significant decrease of its occurrence was also noticed over the time. The S382A/C and A553G existed in 8.4% and 30.8% of the isolates, respectively. In pvmdr1, the mutation Y976F occurred at a low frequency in 5/232 (2.2%), while T958M was fixed and F1076L was approaching fixed (72.4%). The K10 insertion was detected at an occurrence of 33.2% in pvcrt-o, whereas there was no significant difference among the sites or over the time. No mutation was identified in pvk12.

Conclusions

Mutations related with resistance to antifolate drugs are prevalent in this area, while their frequencies decrease significantly with time, suggestive of increased susceptibility of P. vivax parasite to antifolate drugs. Resistance to chloroquine (CQ) is possibly emerging. However, since the molecular mechanisms underneath CQ resistance is yet to be better understood, close supervision of clinical drug efficiency and continuous function investigation is urgently needed to alarm drug resistance.

Graphical abstract
KSR2-14–3-3ζ complex serves as a biomarker and potential therapeutic target in sorafenib-resistant hepatocellular carcinoma
Authors: Gao Chao , Wang Si-wei , Lu Jia-cheng , Chai Xiao-qiang , Li Yuan-cheng , Zhang Peng-fei , Huang Xiao-yong , Cai Jia-bin , Zheng Yi-min , Guo Xiao-jun , Shi Guo-ming , Ke Ai-wu , Fan Jia
Published: April 2022

Background

Kinase suppressor of Ras 2 (KSR2) is a regulator of MAPK signaling that is overactivated in most hepatocellular carcinoma (HCC). We sought to determine the role of KSR2 in HCC pathogenesis.

Methods

We tested the level of KSR2 in HCC tissues and cell lines by tissue microarray, qPCR, and western blotting. Functionally, we determined the effects of KSR2 on the proliferation, migration, and invasion of HCC cells through colony formation assays, scratch assays, transwell migration assays, and xenograft tumor models. Co-immunoprecipitation (co-IP) experiments were used to assess the interaction of phospho-serine binding protein 14–3-3ζ and KSR2, and the effects of this interaction on growth and proliferation of human HCC cells were tested by co-overexpression and knockdown experiments. Additionally, we used flow cytometry to examine whether the KSR2 and 14–3-3ζ interaction conveys HCC resistance to sorafenib.

Results

KSR2 was significantly upregulated in HCC tissues and cell lines, and high KSR2 expression associated with poor prognosis in HCC patients. KSR2 knockdown significantly suppressed HCC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, co-IP experiments identified that 14–3-3ζ complexed with KSR2, and elevated 14–3-3ζ increased KSR2 protein levels in HCC cells. Importantly, Kaplan–Meier survival analysis showed that patients with both high KSR2 and high 14–3-3ζ expression levels had the shortest survival times and poorest prognoses. Interestingly, HCC cells overexpressing both KSR2 and 14–3-3ζ, rather than either protein alone, showed hyperactivated MAPK signaling and resistance to sorafenib.

Conclusions

Our results provide new insights into the pro-tumorigenic role of KSR2 and its regulation of the MAPK pathway in HCC. The KSR2–14–3-3ζ interaction may be a therapeutic target to enhance the sorafenib sensitivity of HCC.
Impact of CEO attributes on corporate reputation, financial performance, and corporate sustainable growth: evidence from India
Authors: Mukherjee Tutun , Sen Som Sankar
Published: April 2022

This article investigates the impact of CEO attributes on corporate reputation, financial performance, and corporate sustainable growth in India. Using static panel data methodology for a sample of NSE listed leading 138 non-financial companies over the time-frame 2011 to 2018, we find that CEO remuneration and tenure maintains significant positive associations with corporate reputation, while duality and CEO busyness are found to be associated with corporate reputation negatively. The results also show that female CEOs and CEO remuneration are associated with corporate financial performance positively, whereas CEO busyness, as expected, holds a significant negative relationship with corporate financial performance. Moreover, the results demonstrate that CEO age is associated with corporate sustainable growth negatively, while tenure appears to have a significant and positive association with corporate sustainable growth. The results are robust to various tests and suggest that in the Indian context, demographic and job-specific attributes of CEOs exert significant influence on corporate reputation, financial performance, and corporate sustainable growth. The empirical findings would provide a basis for the shareholders and companies to identify areas of consideration when appointing CEOs and determining their roles and responsibilities.
Radiolabeled nanomaterials for biomedical applications: radiopharmacy in the era of nanotechnology
Authors: Pijeira Martha Sahylí Ortega , Viltres Herlys , Kozempel Jan , Sakmár Michal , Vlk Martin , İlem-Özdemir Derya , Ekinci Meliha , Srinivasan Seshasai , Rajabzadeh Amin Reza , Ricci-Junior Eduardo , Alencar Luciana Magalhães Rebelo , Al Qahtani Mohammed , Santos-Oliveira Ralph
Published: April 2022

Background

Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. Nanomedicine, a term for the application of nanotechnology in medical and health fields, uses nanoparticles for several applications such as imaging, diagnostic, targeted cancer therapy, drug and gene delivery, tissue engineering, and theranostics.

Results

Here, we overview the current state-of-the-art of radiolabeled nanoparticles for molecular imaging and radionuclide therapy. Nanostructured radiopharmaceuticals of technetium-99m, copper-64, lutetium-177, and radium-223 are discussed within the scope of this review article.

Conclusion

Nanoradiopharmaceuticals may lead to better development of theranostics inspired by ingenious delivery and imaging systems. Cancer nano-theranostics have the potential to lead the way to more specific and individualized cancer treatment.

Graphical abstract
Patient reported outcomes in genital gender-affirming surgery: the time is now
Authors: Agochukwu-Mmonu Nnenaya , Radix Asa , Zhao Lee , Makarov Danil , Bluebond-Langner Rachel , Fendrick A. Mark , Castle Elijah , Berry Carolyn
Published: April 2022

Transgender and non-binary (TGNB) individuals often experience gender dysphoria. TGNB individuals with gender dysphoria may undergo genital gender-affirming surgery including vaginoplasty, phalloplasty, or metoidioplasty so that their genitourinary anatomy is congruent with their experienced gender. Given decreasing social stigma and increasing coverage from private and public payers, there has been a rapid increase in genital gender-affirming surgery in the past few years. As the incidence of genital gender-affirming surgery increases, a concurrent increase in the development and utilization of patient reported outcome measurement tools is critical. To date, there is no systematic way to assess and measure patients’ perspectives on their surgeries nor is there a validated measure to capture patient reported outcomes for TGNB individuals undergoing genital gender-affirming surgery. Without a systematic way to assess and measure patients’ perspectives on their care, there may be fragmentation of care. This fragmentation may result in challenges to ensure patients’ goals are at the forefront of shared- decision making. As we aim to increase access to surgical care for TGNB individuals, it is important to ensure this care is patient-centered and high-quality. The development of patient-reported outcomes for patients undergoing genital gender-affirming surgery is the first step in ensuring high quality patient-centered care. Herein, we discuss the critical need for development of validated patient reported outcome measures for transgender and non-binary patients undergoing genital reconstruction. We also propose a model of patient-engaged patient reported outcome measure development.
Fungal and oomycete pathogens and heavy metals: an inglorious couple in the environment
Authors: Gajewska Joanna , Floryszak-Wieczorek Jolanta , Sobieszczuk-Nowicka Ewa , Mattoo Autar , Arasimowicz-Jelonek Magdalena
Published: April 2022

Heavy metal (HM) contamination of the environment is a major problem worldwide. The rate of global deposition of HMs in soil has dramatically increased over the past two centuries and there of facilitated their rapid accumulation also in living systems. Although the effects of HMs on plants, animals and humans have been extensively studied, yet little is known about their effects on the (patho)biology of the microorganisms belonging to a unique group of filamentous eukaryotic pathogens, i.e., fungi and oomycetes. Much of the literature concerning mainly model species has revealed that HM stress affects their hyphal growth, morphology, and sporulation. Toxicity at cellular level leads to disturbance of redox homeostasis manifested by the formation of nitro-oxidative intermediates and to the induction of antioxidant machinery. Despite such adverse effects, published data is indicative of the fact that fungal and oomycete pathogens have a relatively high tolerance to HMs in comparison to other groups of microbes such as bacteria. Likely, these pathogens may harbor a network of detoxification mechanisms that ensure their survival in a highly HM-polluted (micro)habitat. Such a network may include extracellular HMs immobilization, biosorption to cell wall, and/or their intracellular sequestration to proteins or other ligands. HMs may also induce a hormesis-like phenomenon allowing the pathogens to maintain or even increase fitness against chemical challenges. Different scenarios linking HMs stress and modification of the microorganisms pathogenicity are disscused in this review.
Impact of a health services innovation university program in a major public hospital and health service: a mixed methods evaluation
Authors: Martin Elizabeth , Fisher Olivia , Merlo Gregory , Zardo Pauline , Barrimore Sally E. , Rowland Jeffrey , Davies Janet M.
Published: April 2022

Background

While health services and their clinicians might seek to be innovative, finite budgets, increased demands on health services, and ineffective implementation strategies create challenges to sustaining innovation. These challenges can be addressed by building staff capacity to design cost-effective, evidence-based innovations, and selecting appropriate implementation strategies. A bespoke university award qualification and associated program of activities was developed to build the capacity of staff at Australia’s largest health service to implement and evaluate evidence-based practice (EBP): a Graduate Certificate in Health Science majoring in Health Services Innovation. The aim of this study was to establish the health service’s pre-program capacity to implement EBP and to identify preliminary changes in capacity that have occurred as a result of the Health Services Innovation program.

Methods

A mixed methods design underpinned by the Consolidated Framework for Implementation Research informed the research design, data collection, and analysis. Data about EBP implementation capacity aligned to the framework constructs were sought through qualitative interviews of university and health service executives, focus groups with students, and a quantitative survey of managers and students. The outcomes measured were knowledge of, attitudes towards, and use of EBP within the health service, as well as changes to practice which students identified had resulted from their participation in the program.

Results

The Health Services Innovation program has contributed to short-term changes in health service capacity to implement EBP. Participating students have not only increased their individual skills and knowledge, but also changed their EPB culture and practice which has ignited and sustained health service innovations and improvements in the first 18 months of the program. Capacity changes observed across wider sections of the organization include an increase in connections and networks, use of a shared language, and use of robust implementation science methods such as stakeholder analyses.

Conclusion

This is a unique study that assessed data from all stakeholders: university and health service executives, students, and their managers. By assembling multiple perspectives, we identified that developing the social capital of the organization through delivering a full suite of capacity-building initiatives was critical to the preliminary success of the program.
Non–Small-Cell Lung Cancer With CNS Metastasis: Disparities From a Real-World Analysis (GBOT-LACOG 0417)
Authors: Coelho Juliano Cé , de Souza Carvalho Giselle , Chaves Fabio , de Marchi Pedro , de Castro Jr Gilberto , Baldotto Clarissa , Mascarenhas Eldsamira , Pacheco Patricia , Gomes Rafaela , Werutsky Gustavo , Araujo Luiz H.
Published: April 2022

PURPOSE

Despite the advances in the approach to non–small-cell lung cancer (NSCLC) with CNS metastasis, access to timely diagnosis and treatment may not be optimal in many instances. Our main objective was to describe a cohort of patients with NSCLC with brain metastases from public and private cancer centers, and the differences between patients' presentation, treatment, and outcomes.

METHODS

GBOT-LACOG 0417 is a multi-institutional retrospective cohort study of patients diagnosed with NSCLC and CNS metastasis in Brazil. All patients had confirmed diagnosis of NSCLC between January 2010 and December 2015. CNS metastases were identified by imaging.

RESULTS

A total of 273 patients were included. Patients treated at public institutions were more often Black or Brown (38.8% v 15.4%), current or former smoker (88.6% v 60.0%), of squamous cell histology (25.0% v 9.1%), EGFR- and ALK-negative (95.9% v 74.9%), and were less frequently assessed by using brain magnetic resonance imaging (38.8% v 83.6%). At public institutions, patients were more often symptomatic (78.1% v 44.6%) and had worse performance status (Eastern Cooperative Oncology Group 2 or higher 61.5% v 10.3%). CNS metastases were larger (median size 25 v 15 mm) and more often surrounded by edema (67.7% v 55.2%) at public institutions. Patients at public institutions were more frequently treated with whole-brain radiation therapy (72.9% v 45.4%) and less frequently with radiosurgery (6.3% v 24.1%). Among patients from private care, median overall survival was 24.2 months (95% CI, 20.0 to 30.6), significantly higher than in public care (median 12.1 months; 95% CI, 6.7 to 13.6; P < .001).

CONCLUSION

Our results demonstrate the discrepancy between public and private health care system in the critical setting of patients with CNS metastasis from NSCLC.
Oblique ion-acoustic solitary waves in anisotropic plasma with Tsallis distribution
Authors: Khalid Muhammad
Published: April 2022

The nonlinear propagation of ion-acoustic (IA) solitary waves (SWs) is studied in a magnetized electron-ion (EI) plasma in the presence of pressure anisotropy with Tsallis distribution. The energy integral equation is derived by employing the Sagdeev approach. The present model supports only positive potential nonlinear structures. The effect of relevant plasma parameters on the characteristics of IA solitary structures is investigated. The present investigation could be useful in space and astrophysical plasma systems.
Tumor-induced Osteomalacia: A Systematic Review and Individual Patient’s Data Analysis
Authors: Rendina Domenico , Abate Veronica , Cacace Giuseppe , D’Elia Lanfranco , De Filippo Gianpaolo , Del Vecchio Silvana , Galletti Ferruccio , Cuocolo Alberto , Strazzullo Pasquale
Published: April 2022

Context

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small, benign, and slow-growing phosphaturic mesenchymal tumors. Clinically, TIO is characterized by renal phosphate leak, causing hypophosphatemia and osteomalacia. This review was performed to assess the clinical characteristics of TIO patients described worldwide so far.

Evidence Acquisition

On June 26, 2021, a systematic search was performed in Medline, Google Scholar, Google book, and Cochrane Library using the terms: “tumor induced osteomalacia,” “oncogenic osteomalacia,” “hypophosphatemia.” There were no language restrictions. This review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria.

Evidence Results

Overall, 1725 TIO cases were collected. TIO was more frequent in adult men, who showed a higher incidence of fractures compared with TIO women. The TIO-causing neoplasms were identified in 1493 patients. The somatostatin receptor-based imaging modalities have the highest sensitivity for the identification of TIO-causing neoplasms. TIO-causing neoplasms were equally located in bone and soft tissues; the latter showed a higher prevalence of fractures and deformities. The surgery is the preferred TIO definitive treatment (successful in > 90% of patients). Promising nonsurgical therapies are treatments with burosumab in TIO patients with elevated fibroblast growth factor-23 levels, and with radiolabeled somatostatin analogs in patients with TIO-causing neoplasm identified by somatostatin receptor-based imaging techniques.

Conclusion

TIO occurs preferentially in adult men. The TIO clinical expressiveness is more severe in men as well as in patients with TIO-causing neoplasms located in soft tissues. Treatments with burosumab and with radiolabeled somatostatin analogs are the most promising nonsurgical therapies.
Relating Period and Cohort Fertility
Authors: Schoen Robert
Published: April 2022

From a population perspective, the trajectories of both the total fertility at successive time periods and the total fertility of successive birth cohorts are derived from the same array of age-specific fertility rates. This analysis uses the assumption of constant age-specific fertility proportions to derive new explicit relationships between period and cohort fertility. In short, period total fertility is approximately equal to the total fertility of the cohort born a generation earlier, with a modest additive adjustment. A simple relationship also links both period and cohort total fertility to ACF, the average fertility of the childbearing cohorts in a given year. Assuming that fertility levels follow a cubic curve, cohort values from the derived relationships are then compared to observed cohort fertility values for the United States in 1917–2019. Despite substantial violations of the constant proportional fertility assumption, the calculated values deviate from the observed values by an average of only 7–8%. Short-term projections suggest that U.S. cohort fertility will continue to decline.
Zhen 眞 as the Ideal of Landscape Painting in Bifaji 筆法記
Authors: Kang Yoewool
Published: April 2022

Bifaji 筆法記 by Jing Hao 荊浩 (ca. 855–915) is one of the most critical writings on painting in the Chinese art tradition. It reflects the shifting artistic trends of the late Tang and Five Dynasties periods from portraits to landscapes and from color to ink and wash. The emphasis on zhen (眞, “genuineness”) as an aesthetic goal in Bifaji is an essential feature in its discourse on the nature of painting. This essay explores the concept of zhen as an ideal state of pictorial reality in Bifaji. Illuminating the meaning of zhen is vital to understanding Jing Hao's and his contemporaries' artistic aspirations. Considering its aesthetic connotations reveals zhen in Bifaji to be multivalent, involving a number of qualities required for the creation of a landscape painting, from the observation of nature to the method of brush technique. To elucidate the aesthetic ideals of Bifaji, this paper examines the relationship between the concept of zhen and other key terms such as qiyun (氣韻, “character”), qishi (氣勢, “dynamic configuration”), and xiang (象, “image”) along with the additional conceptual layer of qi applied in the Six Essentials (Liuyao 六要) and the Four Forces (Sishi 四勢).
The Diversity of Confucianism in the Southern Song Dynasty: A Comparative Study of Zhu Xi's and Zhang Shi's Views on Taiji and Human Nature
Authors: Li Lizhu
Published: April 2022

Zhang Shi 張栻 (1133–80), a Confucian scholar of the Southern Song dynasty, has been considered as yielding to Zhu Xi's 朱熹 (1130–1200) ideas in most cases, his own thought exhibiting no specific features. This essay is an attempt to examine the differences between Zhu Xi's and Zhang Shi's supreme pivot (taiji 太極) and nature (xing 性) theories. The features of Zhang Shi's thought and his influence on the neo-Confucianism of the Southern Song dynasty should be reexamined. Some contemporary scholars, including Zhang Shi, have been ignored to a certain degree since Zhu Xi was praised as the representative scholar of neo-Confucianism. This study shows the diversity of neo-Confucianism in the Southern Song dynasty.
The effects of soft and rough substrates on suction-based adhesion
Authors: Huie Jonathan M. , Summers Adam P.
Published: April 2022

The northern clingfish (Gobiesox maeandricus) has a suction-based adhesive disc that can stick to incredibly rough surfaces, a challenge for stiff commercial suction cups. Both clingfish discs and bioinspired suction cups have stiff cores but flexible edges that can deform to overcome surface irregularities. Compliant surfaces are common in nature and technical settings, but performance data for fish and commercial cups are gathered from stiff surfaces. We quantified the interaction between substrate compliance, surface roughness and suction performance for the northern clingfish, commercial suction cups and three biomimetic suction cups with disc rims of varying compliance. We found that all cups stick better on stiffer substrates and worse on more compliant ones, as indicated by peak stress values. On compliant substrates, surface roughness had little effect on adhesion, even for commercial cups that normally fail on hard, rough surfaces. We propose that suction performance on compliant substrates can be explained in part by effective elastic modulus, the combined elastic modulus from a cup–substrate interaction. Of all the tested cups, the biomimetic cups performed the best on compliant surfaces, highlighting their potential to be used in medical and marine geotechnical fields. Lastly, we discuss the overmolding technique used to generate the bioinspired cups and how it is an important tool for studying biology.
Sensitivity of PCR analysis (melting curve method) in diagnosis of Pulmonary Tuberculosis (PTB) based on Bronchoalveolar Lavage (BAL) by bronchoscope
Authors: Wei Jun , Sun Jun , Shuai Xuefen , Ren Junqing , Chen Xuedong
Published: April 2022

Objectives: To evaluate the sensitivity of the real-time PCR assay melting curve method in the diagnosis of pulmonary tuberculosis (PTB) by analyzing bronchoalveolar lavage fluid (BALF) obtained from bronchoscopy.

Methods: A total of 214 PTB patients who were treated at Xuancheng People’s Hospital respiratory and infection department during January 2018 to January 2021 were included in this study. Bronchoscopic bronchoalveolar lavage fluid (BALF) examined by polymerase chain reaction (melting curve method), BALF smear, BALF culture, lipoarabinomannan (LAM) antigen test for diagnosis of tuberculosis (TB) (LAM-TB), acid-fast stain (AFS), and serum adenosine deaminase (ADA) test were conducted respectively to compare their positive predictive values (PPVs).

Results: Of the 214 patients with confirmed PTB, 84.11% were BALF melting curve method positive, significantly higher than the positive results yielded by other PTB screening tests, i.e., LAM-TB (69.16%), AFS (51.87%), ADA (49.07%), BALF culture (62.15%), and BALF smear (41.12%) (p<0.05, respectively). The PPVs were increased to 92.06%, 93.93%, 92.99%, 95.79%, and 91.12% when BALF melting curve method was performed in combination with LAM-TB, AFS, ADA, BALF culture, and BALF smear, respectively, significantly higher than that produced by BALF melting curve method or the combined use of any two of the non-BALF melting curve method tests (p<0.05, respectively).

Conclusion: BALF melting curve method is an ideal diagnostic approach to PTB, which is of a higher diagnostic value compared with LAM-TB, AFS, ADA, BALF culture, and BALF smear.

doi: https://doi.org/10.12669/pjms.38.5.5480

How to cite this:Wei J, Sun J, Shuai X, Ren J, Chen X. Sensitivity of PCR analysis (melting curve method) in diagnosis of Pulmonary Tuberculosis (PTB) based on Bronchoalveolar Lavage (BAL) by bronchoscope. Pak J Med Sci. 2022;38(5):---------.  doi: https://doi.org/10.12669/pjms.38.5.5480

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.
Clinical evaluation of contrast-enhanced CT combined with PET/CT in diagnosis of mediastinal lymph node metastasis of non-small-cell lung cancer
Authors: Li Xiaodong , Zheng Xiaomeng , Zhang Tianle , Dong Xi , Su Jian
Published: April 2022

Objectives: To investigate the clinical value of contrast-enhanced CT combined with PET/CT in the differential diagnosis of mediastinal lymph node metastasis (MLNM) of non-small-cell lung cancer (NSCLC).

Methods: A total of 120 patients with NSCLC combined with mediastinal lymphadenopathy hospitalized in our hospital were selected. All the patients received radical resection of lung cancer and mediastinal lymphadenectomy. After pathological diagnosis, they were divided into MLNM group (malignant group, undergoing contrast-enhanced CT) and non-MLNM group (benign group, receiving contrast-enhanced CT combined with PET-CT). The results were judged by two senior radiologists independently. The results of different scanning methods and postoperative pathology were compared using the t test, χ2 test and Pearson correlation coefficient test.

Results: Compared with the pathological results, contrast-enhanced CT diagnosed 31 cases, with a coincidence rate of 62%, and contrast-enhanced CT combined with PET-CT diagnosed 42 cases, with a coincidence rate of 84%, presenting a statistically significant difference (P = 0.02). Among the 120 patients with lung cancer, pathological examination confirmed MLNM in 50 patients and benign enlargement in 70 patients, contrast-enhanced CT alone detected metastasis in 40 patients and benign enlargement in 80 patients, and contrast-enhanced CT combined with PET-CT detected metastasis in 47 patients and benign enlargement in 73 patients. The sensitivity and accuracy of the latter were significantly higher than those of the former (sensitivity, P = 0.01; accuracy, P = 0.01). With the increase in the malignancy of lymph nodes, the degree of CT enhancement, the concentration of radioactive substances and SUV value increased, showing positive correlations.

Conclusion: Contrast-enhanced CT combined with PET/CT in the diagnosis of MLNM of NSCLC presents higher coincidence rate, sensitivity and accuracy. With the increase in tumor malignancy, the enhancement degree and radioactive substance concentration increase. The two methods are synergistic and complementary in diagnosing MLNM.

doi: https://doi.org/10.12669/pjms.38.5.5528

How to cite this:Li X, Zheng X, Zhang T, Dong X, Su J. Clinical evaluation of contrast-enhanced CT combined with PET/CT in diagnosis of mediastinal lymph node metastasis of non-small-cell lung cancer. Pak J Med Sci. 2022;38(5):---------.  doi: https://doi.org/10.12669/pjms.38.5.5528

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.