bluuebunny/crossref_metadata_2025 huggingface dataset:
Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients
Authors: Sun Xuqi , Mei Jie , Lin Wenping , Yang Ziliang , Peng Wei , Chen Jinbin , Zhang Yaojun , Xu Li , Chen Minshan
Published: July 2021

Background

Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy.

Methods

A total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS.

Results

Among all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade (P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% (p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS (p = 0.003 and 0.006).

Conclusion

Early reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.
Treatment optimization of pelvic external beam radiation and/or vaginal brachytherapy for patients with stage I to II high-risk Endometrioid adenocarcinoma: a retrospective multi-institutional analysis
Authors: Wang Wenhui , Zou Lijuan , Wang Tiejun , Liu Zi , He Jianli , Sun Xiaoge , Zhong Wei , Zhao Fengju , Li Xiaomei , Li Sha , Zhu Hong , Ma Zhanshu , Sun Shuai , Jin Meng , Zhang Fuquan , Hou Xiaorong , Wei Lichun , Hu Ke
Published: July 2021

Background

For stage I to II high-risk endometrioid adenocarcinoma patients, the optimal adjuvant radiotherapy modality remains controversial. The present study sought to optimize the treatment of pelvic external beam radiation (EBRT) with/or vaginal brachytherapy (VBT) for high-risk endometrioid adenocarcinoma patients in multiple radiation oncology centers across China.

Methods

This article retrospectively reviewed stage I to II patients with resected endometrioid adenocarcinoma treated at 13 radiation centers from 1999 to 2015. Patients were eligible if they had high-risk features (stage IB Grade 3 disease or stage II Grade 1–3 disease) on the basis of ESMO-ESGO-ESTRO risk group consensus.

Results

A total of 218 patients were included. Fifty-one patients received EBRT, 25 patients received VBT, and 142 patients were administered EBRT combined with VBT. The three groups were comparable in baseline characteristics, except the proportion of stage IB and Grade 3 disease in the VBT group was significantly higher and their age was older. Survival analysis showed that OS, DFS, LRFS and DMFS were significantly different among the three groups. Two out of three groups were compared with each other, and results demonstrated that DFS, LRFS and DMFS were worse in the VBT group than in the EBRT or EBRT + VBT group. The 3-year OS rates were 95.2, 85.2 and 95.1% in the EBRT, VBT and EBRT + VBT groups, respectively (p = 0.043). There was no significant difference in survival outcomes between EBRT group and EBRT + VBT group. A propensity matching analysis was performed to eliminate group differences. The results demonstrated that DFS and LRFS were significantly improved in the pelvic radiation group compared to the VBT group. Distant failure accounted for most of the failure patterns. Patients in the VBT group had significantly increased local and regional recurrence rates than patients in the EBRT or EBRT + VBT group. Acute and chronic radiation-induced toxicities were well tolerated for all patients.

Conclusion

For patients with postoperative stage I to II high-risk endometrioid adenocarcinoma, compared with VBT alone, radiotherapy modalities including EBRT significantly improved DFS, LRFS and DMFS with tolerable adverse effects. Overall survival was not significantly different between EBRT and EBRT + VBT modalities.
The disposable bandage soft contact lenses therapy and anterior segment optical coherence tomography for management of ocular graft-versus-host disease
Authors: Sun Yi-Chen , Inamoto Yoshihiro , Wang Ruikang K. , Lee Stephanie J. , Hung Kai-Feng , Shen Tueng T.
Published: July 2021

Purpose

To identify the ocular surface changes of ocular graft-versus-host disease (GVHD) using anterior segment optical coherence tomography (AS-OCT) and examine the efficacy of disposable bandage soft contact lens (BSCL) treatment in ocular GVHD patients.

Methods

This study is a prospective, Phase II clinical trial. Nineteen patients diagnosed with chronic GVHD based on the NIH criteria and ocular symptoms of NIH eye score 2 or greater were enrolled. Disposable BSCL was applied to the GVHD-affected eyes with topical antibiotic coverage. Ocular exams, eye symptom surveys, and AS-OCT were performed with signed informed consent. Patients were followed for one to three months.

Results

Thirty-eight eyes of 19 patients with ocular GVHD underwent BSCL treatment in this study. AS-OCT scans were done in 14 out of 19 patients. The mean best-corrected visual acuity at enrollment, 2-week, and 4-week visits was 0.180, 0.128, and 0.163 logMAR, respectively. Twenty-four out of 25 eyes (96 %) that initially presented with conjunctival inflammation, twenty-three out of 30 eyes (76.7 %) that initially presented with punctate epithelial erosion, and 8 out of 15 (53.3 %) eyes that initially presented with filamentous keratopathy showed improvement after wearing BSCL for 2 to 4 weeks. AS-OCT revealed corneal epithelial irregularity, abnormal meibomian gland orifice, and conjunctival hyperemia, in patients with ocular GVHD.

Conclusions

BSCL treatment provided significant subjective and objective improvements in ocular GVHD patients. Meanwhile, we found that AS-OCT can be a promising diagnostic tool to characterize the ocular surface changes associated with ocular GVHD.
Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?
Authors: Purushothaman Vidya Lakshmi , Cuomo Raphael E. , Garland Cedric F. , Mackey Timothy K.
Published: July 2021

Background

Vitamin D has been identified as a potential protective factor in the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally.

Methods

In this ecological study, a series of linear and polynomial regression tests were performed between country-specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps.

Results

The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates.

Conclusion

The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population-wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.
Factors associated with the intention of Syrian adult population to accept COVID19 vaccination: a cross-sectional study
Authors: Mohamad Okbah , Zamlout Ali , AlKhoury Naseem , Mazloum Abd Aljawad , Alsalkini Marah , Shaaban Rafea
Published: July 2021

Background and objectives

With global efforts to develop and deliver a COVID-19 vaccine rapidly, vaccine hesitancy stands as a barrier to these efforts. We aimed to estimate the proportion of Syrian adult population intending to be vaccinated against COVID-19 and, principally, to assess the demographic and attitudinal factors associated with it in order to approach suitable solutions.

Methods

An anonymous online questionnaire was conducted between 23rd December 2020 and 5th January 2021 in various provinces in Syria. A total of 3402 adults were sampled to reflect the population demographic factors. Attitudinal factors included Covid-19 fears, risks, and beliefs on the origin. Vaccination hesitancy and knowledge were also measured. The intention to get vaccinated against COVID-19 was the primary endpoint.

Results

According to their statements, 1222 participants (35.92%) will consent to get vaccinated against COVID-19. Our findings indicate that male gender, younger age, rural residence, not having children, smoking, fear about COVID-19, individual perceived severity, believing in the natural origin of the coronavirus, and high vaccination knowledge were positive predictors of embracing COVID-19 vaccine when it is available.

Conclusion

COVID-19 vaccine acceptance rate is considerably poor across Syrian population compared to populations in developed countries. Vaccine hesitancy is closely bound to the fear of side effects and doubts about vaccine efficacy. Factors such as conspiracy beliefs and myths about the vaccine lower vaccine uptake. Thus, interventional educational campaigns are increasingly required to overcome misinformation and avert low vaccination acceptance rates.
Understanding and managing HIV infection risk among men who have sex with men in rural Uganda: a qualitative study
Authors: Nakiganda Lydia Jacenta , Bell Stephen , Grulich Andrew E. , Serwadda David , Nakubulwa Rosette , Poynten Isobel Mary , Bavinton Benjamin R.
Published: July 2021

Background

Same-sex sexual relations are criminalised in Uganda, and men who have sex with men (MSM) experience a high burden of HIV infection. In Uganda, health promotion policies focus on equity in healthcare and creating enabling environments. At present there is limited evidence upon which to enhance engagement of MSM in rural settings into effective HIV prevention. To fill this gap, our study explored MSM’s understandings of HIV risk and strategies used to reduce HIV risk in their sexual lives.

Methods

In-depth interviews were conducted with sixteen MSM in rural communities in Southwestern Uganda. Inductive thematic analysis examined men’s perceptions of HIV risk and strategies of reducing their own HIV risks.

Results

Understandings of HIV risk and risk practices were framed by lack of access to condoms, challenges negotiating condom and pre-exposure prophylaxis (PrEP) use, and condomless sex being reported as more pleasurable than sex with condoms. Strategies men perceived as enabling them to manage HIV risk included: PrEP use; condom use; knowing partners’ HIV status; avoiding partners associated with HIV risk; oral sex; withdrawal before ejaculation and washing one’s penis after sex. There were several misconceptions arising from poor HIV prevention knowledge. Strategies reliant on communication and negotiation with sexual partners were inhibited by gendered powered imbalances.

Conclusions

Our findings illustrate that MSM in rural settings in Uganda are making concerted efforts to implement strategies that might reduce risk of HIV transmission and infection within their sexual relationships. Key HIV health promotion and service-related strategies to support MSM with these efforts include an effective condom and lubricant supply chain; a PrEP program in trusted local health units, implemented via discreet community-outreach mechanisms; and same-sex specific HIV-related health promotion.
Potentials of community-based early detection of cardiovascular disease risk during the COVID-19 pandemic
Authors: Siregar Kemal Nazarudin , Kurniawan Rico , BaharuddinNur Ryza Jazid , Nuridzin Dion Zein , Handayani Yolanda , Retnowati  , Rohjayanti  , Halim Lindawati
Published: July 2021

Background

The Coronavirus Disease 2019 (COVID-19) pandemic has led to a significant decline in Non Communicable Diseases (NCD) screening and early detection activities, especially Cardiovascular Disease (CVD). This study aims to assess the potential of community-based self-screening of CVD risk through the mhealth application.

Methods

This is operational research by actively involving the community to carry out self-screening through the mHealth application. Community health workers were recruited as facilitators who encourage the community to carry out self-screening. To evaluate the potential of community-based self-screening of CVD risk, we use several indicators: responses rate, level of CVD risk, and community acceptance.

Results

Of the 846 individuals reached by the cadres, 53% or 442 individuals carried out self-screening. Based on the results of self-screening of CVD risk, it is known that around 21.3% are at high risk of developing CVD in the next 10 years. The results of the evaluation of semi-structured questions showed that about 48% of the people had positive impressions, 22% assessed that this self-screening could increase awareness and was informative, 3% suggested improvements to self-screening tools.

Conclusion

Cadres play an important role in reaching and facilitating the community in their environment to remain aware of their health conditions by conducting self-screening of CVD risk. The availability of the mHealth application that the public can easily access can simplify CVD risk prediction and expand screening coverage, especially during the COVID-19 pandemic, where there are social restrictions policies and community activities.
Proximal gastrectomy with gastric tube reconstruction or jejunal interposition reconstruction in upper-third gastric cancer: which offers better short-term surgical outcomes?
Authors: Li Zhiguo , Ma Yan , Liu Guiting , Fang Ming , Xue Yingwei
Published: July 2021

Objective

Proximal gastrectomy acts as a function-preserving operation for upper-third gastric cancer. The aim of this study was to compare the short-term surgical outcomes between proximal gastrectomy with gastric tube reconstruction and proximal gastrectomy with jejunal interposition reconstruction in upper-third gastric cancer.

Methods

A retrospective review of 301 patients who underwent proximal gastrectomy with jejunal interposition (JI) or gastric tube (GT) at Harbin Medical University Cancer Hospital between June 2007 and December 2016 was performed. The Gastrointestinal Symptom Rating Scale (GSRS) and Visick grade were used to evaluate postgastrectomy syndromes. Gastrointestinal fiberoscopy was used to evaluate the prevalence and severity of reflux esophagitis based on the Los Angeles (LA) classification system.

Results

The JI group had a longer operation time than the GT group (220 ± 52 vs 182 ± 50 min), but no significant difference in blood loss was noted. Compared to the GT group, the Visick grade and GSRS score were significantly higher. Reflux esophagitis was significantly increased in the GT group compared with the JI group.

Conclusion

Proximal gastrectomy is well tolerated with excellent short-term outcomes in patients with upper-third gastric cancer. Compared with GT construction, JI construction has clear functional advantages and may provide better quality of life for patients with upper-third gastric cancer.
Media framing of emergency departments: a call to action for nurses and other health care providers
Authors: Thomas Kimberley , Browne Annette J. , Jiao Sunny , Dooner Caryn , Wright Patrice , Slemon Allie , Diederich Jennifer , Wathen C. Nadine , Bungay Vicky , Wilson Erin , Varcoe Colleen
Published: July 2021

Background

As part of a larger study focused on interventions to enhance the capacity of nurses and other health care workers to provide equity-oriented care in emergency departments (EDs), we conducted an analysis of news media related to three EDs. The purpose of the analysis was to examine how media writers frame issues pertaining to nursing, as well as the health and social inequities that drive emergency department contexts, while considering what implications these portrayals hold for nursing practice.

Methods

We conducted a search of media articles specific to three EDs in Canada, published between January 1, 2018 and May 1, 2019. Media items (N = 368) were coded by story and theme attributes. A thematic analysis was completed to understand how writers in public media present issues pertaining to nursing practice within the ED context.

Results

Two overarching themes were found. First, in ED-related media that portrays health care needs of people experiencing health and social inequities, messaging frequently perpetuates stigmatizing discourses. Second, media writers portray pressures experienced by nurses working in the ED in a way that evades structural determinants of quality of care. Underlying both themes is an absence of perspectives and authorship from practicing nurses themselves.

Conclusions

We recommend that frontline nurses be prioritized as experts in public media communications. Nurses must be supported to gain critical media skills to contribute to media, to destigmatize the health care needs of people experiencing inequity who attend their practice, and to shed light on the structural causes of pressures experienced by nurses working within emergency department settings.
Determinants of community pharmacy utilisation among the adult population in Malaysia: findings from the National Health and Morbidity Survey 2019
Authors: Hamidi Normaizira , Tan Yeung R’ong , Jawahir Suhana , Tan Ee Hong
Published: July 2021

Background

Community pharmacies provide alternatives for medication procurement and other basic and minor health-related services in addition to mainstream hospitals and primary healthcare services. This study aimed to determine the characteristics of community pharmacy users and associated factors for community pharmacy utilisation in Malaysia.

Methods

Secondary data analysis was performed using data from the National Health and Morbidity Survey 2019, a nationwide cross-sectional household survey that used a two-stage stratified random sampling design. Adults aged 18 years and over were included in the analysis. Respondents who reported visiting the community pharmacy for health purposes two weeks prior to the study were considered as users. Complex sample descriptive statistics were used to describe the respondents’ characteristics. Logistic regression analyses were employed to determine factors associated with community pharmacy utilisation.

Results

Of the 11,155 respondents interviewed, 10.3 % reported community pharmacy utilisation for health purposes. Females (OR = 1.41, 95 % CI = 1.14, 1.73), those with tertiary education (OR = 2.03, 95 % CI = 1.26, 3.29), urban dwellers (OR = 1.42, 95 % CI = 1.13, 1.79), and those with self-reported health problems (OR = 7.62, 95 % CI = 6.05, 9.59) were more likely to utilise the community pharmacy.

Conclusions

Demographic and socioeconomic factors were important determinants of community pharmacy utilisation in Malaysia with sex, age, education level, locality, and self-reported health problems as the associated factors. These findings serve as evidence for policy interventions, crucial for improvements in accessibility to healthcare services.
Characteristics of the ideal hospitalist inpatient care program: perceptions of Canadian health system leaders
Authors: Yousefi Vandad , McIvor Elayne
Published: July 2021

Background

Despite the growing prevalence of hospitalist programs in Canada, it is not clear what program features are deemed desirable by administrative and medical leaders who oversee them. We aimed to understand perceptions of a wide range of healthcare administrators and frontline providers about the implementation and necessary characteristics of a hospitalist service.

Methods

We conducted semi-structured interviews with a range of administrators, medical leaders and frontline providers across three hospital sites operated by an integrated health system in British Columbia, Canada.

Results

Most interviewees identified the hospitalist model as the ideal inpatient care service line, but identified a number of challenges. Interviewees identified the necessary features of an ideal hospitalist service to include considerations for program design, care and non-clinical processes, and alignment between workload and physician staffing. They also identified continuity of care as an important challenge, and underlined the importance of communication as an important enabler of implementation of a new hospitalist service.

Conclusions

Most hospital administrators and frontline providers in our study believed the hospitalist model resulted in improvements in clinical processes and work environment.
Neonatal heel prick screening TSH concentration in the Netherlands as indicator of iodine status
Authors: Verkaik-Kloosterman Janneke
Published: July 2021

Background

Neonatal Thyroid Stimulating Hormone (nTSH) is proposed as indicator of iodine deficiency in a population. Population’s iodine sufficiency is indicated by a proportion of the newborns less than 3% having nTSH above 5 mIU/L. The aim of this study was to explore the Dutch neonatal heel prick screening TSH data to assess iodine status in the Netherlands and identify determinants and potential confounders of this assessment.

Methods

All newborns born in the Netherlands between 2007 and 2015 with a heel prick collection at day 3-7 were included (n = 1,435,600), except preterm neonates and baby’s with a low birth weight. Total T4 was measured for all children, nTSH was measured in the ~ 20% children with lowest total T4.

Results

The proportion with nTSH > 5mIU/L fluctuated between 0.6-1.3% in 2007-2015. nTSH was significantly associated with laboratory performing the nTSH assay and age of heel prick sampling. The overall increasing trend in proportion nTSH >1mIU/L was confounded by the laboratories with different and changed assays.

Conclusions

The low proportion neonates with high nTSH suggests a sufficient iodine status in the Netherlands. Whether the increased proportion nTSH>1mIU/L over the years is an early indicator of deterioration of the iodine status remains unclear, due to differences and changes in analytical assays. nTSH might be a valuable and inexpensive way to get crude insight in the (trend in) iodine status, but more research is needed on the validity and potential conditions.
Long non-coding RNA SDCBP2-AS1 delays the progression of ovarian cancer via microRNA-100-5p-targeted EPDR1
Authors: Liu Xiu , Liu Chanyuan , Zhang Aijun , Wang Qi , Ge Jiao , Li Qunying , Xiao Jinlei
Published: July 2021

Background

Dysregulation of long non-coding RNAs has been implied to connect with cancer progression. This research was to decipher the mechanism of long non-coding RNA SDCBP2-AS1 in ovarian cancer (OC) through regulation of microRNA (miR)-100-5p and ependymin-related protein 1 (EPDR1).

Methods

LncRNA SDCBP2-AS1 and EPDR1 levels in OC were assessed by Gene Expression Profiling Interactive Analysis. lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 levels in OC tissues and cells were determined. SKOV3 and A2780 cells were transfected with lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1-related plasmids or sequences, and then their functions in cell viability, apoptosis, migration, and invasion were evaluated. The interplay of lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 was clarified.

Results

LncRNA SDCBP2-AS1 and EPDR1 levels were suppressed whilst miR-100-5p level was elevated in OC. After upregulating lncRNA SDCBP2-AS1 or EPDR1, viability, migration, and invasion of OC cells were impaired, and apoptosis rate was increased. Downregulating EPDR1 or upregulating miR-100-5p partially mitigated upregulated lncRNA SDCBP2-AS1-induced impacts on the biological functions of OC cells. LncRNA SDCBP2-AS1 sponged miR-100-5p, and EPDR1 was targeted by miR-100-5p.

Conclusion

It is illustrated that lncRNA SDCBP2-AS1 regulates EPDR1 by sponge adsorption of miR-100-5p to inhibit the progression of OC.
Safety and effectiveness evaluation of a two-handed technique combining harmonic scalpel and laparoscopic Peng’s multifunction operative dissector in laparoscopic hemihepatectomy
Authors: Cai Jingwei , Jiang Guixing , Liang Yuelong , Xie Yangyang , Zheng Junhao , Liang Xiao
Published: July 2021

Objectives

This study was designed to evaluate the safety and effectiveness of a two-hand technique combining harmonic scalpel (HS) and laparoscopic Peng’s multifunction operative dissector (LPMOD) in patients who underwent laparoscopic hemihepatectomy (LHH).

Methods

We designed and conducted a case-control study nested in a prospectively collected laparoscopic liver surgery database. Patients who underwent LHH for liver parenchyma transection using HS + LPMOD were defined as cases (n = 98) and LPMOD only as controls (n = 47) from January 2016 to May 2018. Propensity score matching (1:1) between the case and control groups was used in the analyses.

Results

The case group had significantly less intraoperative blood loss in milliliters (169.4 ± 133.5 vs. 221.5 ± 176.3, P = 0.03) and shorter operative time in minutes (210.5 ± 56.1 vs. 265.7 ± 67.1, P = 0.02) comparing to the control group. The conversion to laparotomy, postoperative hospital stay, resection margin, the mean peak level of postoperative liver function parameters, bile leakage rate, and others were comparable between the two groups. There was no perioperative mortality.

Conclusions

We demonstrated that the two-handed technique combing HS and LPMOD in LHH is safe and effective which is associated with shorter operative time and less intraoperative blood loss compared with LPMOD alone. The technique facilitates laparoscopic liver resection and is recommended for use.
Cognitive and brain cytokine profile of non-demented individuals with cerebral amyloid-beta deposition
Authors: Flores-Aguilar Lisi , Iulita M. Florencia , Orciani Chiara , Tanna Neil , Yang Jingyun , Bennett David A. , Cuello A. Claudio
Published: July 2021

Background

Brain inflammation has been increasingly associated with early amyloid accumulation in Alzheimer’s disease models; however, evidence of its occurrence in humans remains scarce. To elucidate whether amyloid deposition is associated with neuroinflammation and cognitive deficits, we studied brain inflammatory cytokine expression and cognitive decline in non-demented elderly individuals with and without cerebral amyloid-beta deposition.

Methods

Global cognition, episodic, working, and semantic memory, perceptual speed, visuospatial ability, and longitudinal decline (5.7 ± 3.6 years) in each cognitive domain were compared between elderly individuals (66–79 years) with and without cerebral amyloid-beta deposition. The expression of 20 inflammatory cytokines was analyzed in frozen temporal, parietal, and frontal cortices and compared between older individuals with and without amyloid-beta deposition in each brain region. Correlation analyses were performed to analyze associations between amyloid-beta load, cytokine expression, and cognitive decline.

Results

Individuals with cortical amyloid-beta deposition displayed deficits and a faster rate of cognitive decline in perceptual speed as compared with those individuals without amyloid-beta. This decline was positively associated with cortical amyloid-beta levels. Elderly individuals with amyloid-beta deposition had higher levels of IL-1β, IL-6, and eotaxin-3 in the temporal cortex accompanied by an increase in MCP-1 and IL-1β in the parietal cortex and a trend towards higher levels of IL-1β and MCP-1 in the frontal cortex as compared with age-matched amyloid-free individuals. Brain IL-1β levels displayed a positive association with cortical amyloid burden in each brain region. Finally, differential cytokine expression in each cortical region was associated with cognitive decline.

Conclusions

Elderly individuals with amyloid-beta neuropathology but no symptomatic manifestation of dementia, exhibit cognitive decline and increased brain cytokine expression. Such observations suggest that increased cytokine expression might be an early event in the Alzheimer’s continuum.
An ectopic adrenocortical oncocytic adenoma in the liver highly mimicking hepatocellular carcinoma: case report and literature review
Authors: Chen Jingci , Wan Xueshuai , Lu Yao , Wang Wenze , Zhao Dachun , Lu Zhaohui , Mao Yilei , Chen Jie
Published: July 2021

Background

Ectopic adrenocortical tissue is a lesion usually found incidentally during autopsy or inguinal surgery. Here, we demonstrate an extremely unusual case of intrahepatic adrenocortical adenoma which highly mimicks hepatocellular carcinoma (HCC) and brings challenges for clinicians and pathologists. The diagnostic pitfalls have been discussed in detail to provide clues for guiding differential diagnosis and future treatment.

Case presentation

A 44-year-old man was admitted into our hospital for evaluation of a hepatic mass identified during routine examination. Enhanced CT revealed its margin displayed apparent enhancement in arterial phase, but hypointensity in portal and delayed phase. HCC was suspected and partial hepatectomy was performed. Microscopically, cells were arranged in solid sheets. Most of the tumor cells were large, polygonal, had prominent nucleoli and were rich in eosinophilic cytoplasm. Pleomorphic nucleus was frequently found. Focally, smaller cells were found with small nuclei and granular cytoplasm. Immunohistochemically, tumor cells were negative for Arg-1, glypican-3 (GPC3), hepatocyte specific antigen (HSA), and positive for synaptophysin (Syn), α-inhibin, and Melan A. The Ki-67 index was 1 %. The final diagnosis was ectopic adrenocortical oncocytic adenoma and the patient was uneventful after the surgery.

Conclusion

Intrahepatic adrenocortical adenoma in the liver can hardly be diagnosed through radiology and little experience in pathology has been reported. In the present case, massive oncocytic changes and huge pleomorphism add greatly to the difficulties of making correct diagnosis. This lesion should be carefully kept in mind and a combination of markers is suggested for differentiating from HCC.
Identification of immune-infiltrating cell-related biomarkers in hepatocellular carcinoma based on gene co-expression network analysis
Authors: Hou Yinghui , Zhang Guizhi
Published: July 2021

Background

Hepatocellular carcinoma (HCC) is often caused by chronic liver infection or inflammation. Searching for potential immunotherapy targets will aid the early diagnosis and treatment of HCC.

Methods

Firstly, detailed HCC data were downloaded from The Cancer Genome Atlas database. GDCRNATools was used for the comprehensive analysis of RNA sequencing data. Subsequently, the CIBERSORT package was used to estimate infiltration scores of 22 types of immune cells in complex samples. Furthermore, hub genes were identified via weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis. In addition, multiple databases were used to validate the expression of hub gene in the tumor tissue. Finally, prognostic, diagnostic and immunohistochemical analysis of key hub genes was performed.

Results

In the present study, 9 hub genes were identified using WGCNA and PPI network analysis. Furthermore, the expression levels of 9 genes were positively correlated with the infiltration levels of CD8-positive T (CD8+ T) cells. In multiple dataset validations, the expression levels of CCL5, CXCR6, CD3E, and LCK were decreased in cancer tissues. In addition, survival analysis revealed that patients with LCK low expression had a poor survival prognosis (P < 0.05). Immunohistochemistry results demonstrated that CCL5, CD3E and LCK were expressed at low levels in HCC cancer tissues.

Conclusion

The identification of CCL5, CXCR6, CD3E and LCK may be helpful in the development of early diagnosis and therapy of HCC. LCK may be a potential prognostic biomarker for immunotherapy for HCC.
The pathological features of leukemic cells infiltrating the renal interstitium in chronic lymphocytic leukemia/small lymphocytic lymphoma from a large single Chinese center
Authors: Wang Hui , Yu Xiaojuan , Zhang Xu , Wang Suxia , Zhao Minghui
Published: July 2021

Background

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare in Asians, and patients with CLL/SLL seldomly undergo kidney biopsy. The histopathological features and clinical relevance of tubulointerstitial injury in CLL/SLL have not been extensively characterized. Hence, we attempted to describe the clinical characteristics, renal pathology and clinical outcome of a well-characterized population of CLL/SLL patients with CLL cell infiltration in the renal interstitium from a large single center in China.

Methods

Between January 1st, 2010 and September 31st, 2020, 31946renal biopsies were performed at Peking University First Hospital, and 10 CLL/SLL patients with CLL cell infiltration in the renal interstitium were included. Complete clinical data were collected from these 10 patients, and renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy.

Results

The extent of the infiltrating CLL cells in patients with CLL/SLL varied among different patients and ranged from 10 to 90% of kidney parenchyma. Six (60%) of 10 patients presented with an extent of infiltrating CLL cells ≥50%. Interestingly, we found that three patients (3/10, 30%) expressed monoclonal immunoglobulins in the infiltrating CLL cells, and special cytoplasmic crystalline structures were found in two of the three patients by electron microscopy for the first time. Severe renal insufficiency (Scr ≥200 μmol/L) was associated with ≥50% interstitial infiltration of CLL cells in the renal interstitium.

Conclusions

The current study confirmed that CLL cells infiltrating the renal interstitium can directly secrete monoclonal immunoglobulins, indicating that the interstitial infiltrating CLL cells possibly cause renal injury directly by secreting monoclonal immunoglobulins in situ. This finding may prove a new clue to elucidate the pathogenetic mechanism of renal injury involved with CLL/SLL.
Multiple cardiac rhabdomyomas not associated with tuberous sclerosis in a dizygotic twins: a case report
Authors: Yamamoto Koji , Maki Yohei , Sato Yuichiro , Tanaka Hiroyuki , Fukushima Tsuyoshi , Ushijima Junko , Furukawa Seishi , Sameshima Hiroshi , Kataoka Hiroaki
Published: July 2021

Background

Rhabdomyomas comprise the majority of cardiac tumors in fetuses and are found in association with tuberous sclerosis complex. More than 90% of fetuses and neonates with multiple cardiac rhabdomyomas have signs of tuberous sclerosis complex. However, solitary cardiac rhabdomyoma cases are largely unrelated to tuberous sclerosis complex. Here, we report a case involving multiple cardiac rhabdomyomas not associated with tuberous sclerosis complex in a dizygotic twin.

Case presentation

A 36-year-old Japanese woman was diagnosed with a dizygotic twin pregnancy in the first trimester. Consistent with dizygosity, the fetal sex was discordant (male and female). At 27 weeks of gestation, hydrops and multiple echogenic cardiac masses were noted in the male baby, with the largest mass measuring 34 × 30 mm. The female fetus appeared normal. The cardiac masses enlarged gradually with the progression of the hydrops. At 32 weeks of gestation, intrauterine death of the male fetus was confirmed. The next day, autopsy of the male fetus was performed after cesarean section. Three well-demarcated white-tan-colored nodules were formed in the ventricular walls and interventricular septum, with the largest nodule (40 × 30 mm) in the left ventricular wall. Histologically, these lesions were diagnosed as rhabdomyomas.

Conclusions

We encountered a case involving multiple cardiac rhabdomyomas arising in one of dizygotic twin fetuses. Unlike most reported cases of multiple cardiac rhabdomyomas, this case was not accompanied by tuberous sclerosis complex. To the best of our knowledge, this is the first case report of multiple cardiac rhabdomyomas that developed in only one of dizygotic twins in the English literature.
Prevalence of polypharmacy and associated adverse health outcomes in adult patients with chronic kidney disease: protocol for a systematic review and meta-analysis
Authors: Okpechi Ikechi G. , Tinwala Mohammed M. , Muneer Shezel , Zaidi Deenaz , Ye Feng , Hamonic Laura N. , Khan Maryam , Sultana Naima , Brimble Scott , Grill Allan , Klarenbach Scott , Lindeman Cliff , Molnar Amber , Nitsch Dorothea , Ronksley Paul , Shojai Soroush , Soos Boglarka , Tangri Navdeep , Thompson Stephanie , Tuot Delphine , Drummond Neil , Mangin Dee , Bello Aminu K.
Published: July 2021

Background

Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population.

Methods/design

We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran’s Q and I2 index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity).

Discussion

Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD.

Systematic review registration

PROSPERO registration number: [CRD42020206514].
Limits and benefits of participatory agenda setting for research and innovation
Authors: Gudowsky Niklas
Published: July 2021

Current governance of science, technology and innovation (STI) faces tough challenges to meet demands arising from complex issues such as societal challenges or targets, e.g. the United Nations’ Sustainable Development Goals. For decades, scholars and civil society institutions have called for increased public participation in STI, and political institutions have been taking up the request to integrate engagement activities into their decision-making processes, at least in the form of consultations. Moving engagement in research and development further upstream makes early interventions and social shaping of technologies and innovation possible. Since research has also faced repeated requests towards taking on more responsibility for solving societal problems, engagement processes thus help in shaping research. Here, the earliest point for possible engagement can be found within the constituting phase of research agendas as topics, general lines of enquiry and targets are shaped in this phase. These are the boundaries in between which researchers later navigate. This article serves as introduction to this journal’s topical collection on participatory agenda setting for research and innovation (PASE). It provides a review of the literature on theory and practice of PASE activities, summarises the topical collection’s contributions regarding current international cases and analyses respective PASE limits and benefits, thereby promoting its conceptual and practical understanding.
The use of digital twins in healthcare: socio-ethical benefits and socio-ethical risks
Authors: Popa Eugen Octav , van Hilten Mireille , Oosterkamp Elsje , Bogaardt Marc-Jeroen
Published: July 2021

Anticipating the ethical impact of emerging technologies is an essential part of responsible innovation. One such emergent technology is the digital twin which we define here as a living replica of a physical system (human or non-human). A digital twin combines various emerging technologies such as AI, Internet of Things, big data and robotics, each component bringing its own socio-ethical issues to the resulting artefacts. The question thus arises which of these socio-ethical themes surface in the process and how they are perceived by stakeholders in the field. In this report we present the results of a qualitative study into the socio-ethical benefits and socio-ethical risks of using digital twins in healthcare. Employing insights from ethics of technology and the Quadruple Helix theory of innovation, we conducted desk research of white literature and 23 interviews with representatives from the four helixes: industry, research, policy and civil society. The ethical scan revealed several important areas where the digital twin can produce socio-ethical value (e.g., prevention and treatment of disease, cost reduction, patient autonomy and freedom, equal treatment) but also several important areas of socio-ethical risks (e.g., privacy and property of data, disruption of existing societal structures, inequality and injustice). We conclude with a reflection on the employed analytical tool and suggestions for further research.
Applications of artificial intelligence and machine learning in orthodontics: a scoping review
Authors: Bichu Yashodhan M. , Hansa Ismaeel , Bichu Aditi Y. , Premjani Pratik , Flores-Mir Carlos , Vaid Nikhilesh R.
Published: July 2021

Introduction

This scoping review aims to provide an overview of the existing evidence on the use of artificial intelligence (AI) and machine learning (ML) in orthodontics, its translation into clinical practice, and what limitations do exist that have precluded their envisioned application.

Methods

A scoping review of the literature was carried out following the PRISMA-ScR guidelines. PubMed was searched until July 2020.

Results

Sixty-two articles fulfilled the inclusion criteria. A total of 43 out of the 62 studies (69.35%) were published this last decade. The majority of these studies were from the USA (11), followed by South Korea (9) and China (7). The number of studies published in non-orthodontic journals (36) was more extensive than in orthodontic journals (26). Artificial Neural Networks (ANNs) were found to be the most commonly utilized AI/ML algorithm (13 studies), followed by Convolutional Neural Networks (CNNs), Support Vector Machine (SVM) (9 studies each), and regression (8 studies). The most commonly studied domains were diagnosis and treatment planning—either broad-based or specific (33), automated anatomic landmark detection and/or analyses (19), assessment of growth and development (4), and evaluation of treatment outcomes (2). The different characteristics and distribution of these studies have been displayed and elucidated upon therein.

Conclusion

This scoping review suggests that there has been an exponential increase in the number of studies involving various orthodontic applications of AI and ML. The most commonly studied domains were diagnosis and treatment planning, automated anatomic landmark detection and/or analyses, and growth and development assessment.
Assessment of beef carcass contamination with Salmonella and E. coli O 157 in slaughterhouses in Bishoftu, Ethiopia
Authors: Gutema Fanta D. , Abdi Reta D. , Agga Getahun E. , Firew Seyoum , Rasschaert Geertrui , Mattheus Wesley , Crombe Florence , Duchateau Luc , Gabriël Sarah , De Zutter Lieven
Published: July 2021

Background

Salmonella and E. coli O157 are common causes of foodborne diseases. Evisceration and de-hiding steps can lead to carcass contamination during slaughter operation. In Ethiopia, information on the association between the presence of these pathogens in the rectal content and/or on the hide of cattle and their presence on the carcass is lacking.

Methods

The aim of this study was to assess the sources of beef carcass contamination with Salmonella and E. coli O157 during slaughter. Rectal contents and hide- and carcass-swabs (from three sites: foreleg, brisket and hind leg) were collected from 70 beef cattle at two small scale slaughterhouses. Isolates were genotyped by the Pulsed Field Gel Electrophoresis method and tested for resistance against 14 microbial drugs.

Results

Salmonella was detected at equal proportions (7.1%) in rectal content samples and hide swabs. E. coli O157 was detected in 8.6% of the rectal contents and 4.3% of the hide swabs. The proportion of contaminated carcasses was 8.6% for Salmonella and 7.1% for E. coli O157. Genetic linkage between the Salmonella and E. coli O157 isolates from the rectal contents and/or hides and carcasses were observed only in a few cases (2 and 1 carcasses, respectively) indicating the limited direct transfer of the pathogens from the feces and/or hide to the carcass during slaughter. Most carcasses became positive by cross contamination. All the S. Typhimurium isolates (n = 8) were multidrug resistant being resistant to ampicillin, chloramphenicol, sulfamethoxazole and tetracycline. The two S. Dublin isolates were resistant to colistin. All E. coli O157 isolates were susceptible to the antimicrobials tested.

Conclusion

The results indicated that cross contamination may be an important source for carcass contamination.