bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell spheroids are as effective as single cells suspensions in the treatment of critical-sized bone defects
Authors: Findeisen Lisa , Bolte Julia , Vater Corina , Petzold Cathleen , Quade Mandy , Müller Lars , Goodman Stuart B. , Zwingenberger Stefan
Published: May 2021

Background

Due to their multilineage potential and high proliferation rate, mesenchymal stem cells (MSC) indicate a sufficient alternative in regenerative medicine. In comparison to the commonly used 2-dimensional culturing method, culturing cells as spheroids stimulates the cell-cell communication and mimics the in vivo milieu more accurately, resulting in an enhanced regenerative potential. To investigate the osteoregenerative potential of MSC spheroids in comparison to MSC suspensions, cell-loaded fibrin gels were implanted into murine critical-sized femoral bone defects.

Methods

After harvesting MSCs from 4 healthy human donors and preculturing and immobilizing them in fibrin gel, cells were implanted into 2 mm murine femoral defects and stabilized with an external fixator. Therefore, 26 14- to 15-week-old nu/nu NOD/SCID nude mice were randomized into 2 groups (MSC spheroids, MSC suspensions) and observed for 6 weeks. Subsequently, micro-computed tomography scans were performed to analyze regenerated bone volume and bone mineral density. Additionally, histological analysis, evaluating the number of osteoblasts, osteoclasts and vessels at the defect side, were performed.

Statistical analyzation was performed by using the Student’s t-test and, the Mann-Whitney test. The level of significance was set at p = 0.05.

Results

μCT-analysis revealed a significantly higher bone mineral density of the MSC spheroid group compared to the MSC suspension group. However, regenerated bone volume of the defect side was comparable between both groups. Furthermore, no significant differences in histological analysis between both groups could be shown.

Conclusion

Our in vivo results reveal that the osteo-regenerative potential of MSC spheroids is similar to MSC suspensions.
Primary hemiarthroplasty after unstable trochanteric fracture in elderly patients: mortality, readmission and reoperation
Authors: Lin Tzu-Chieh , Wang Pin-Wen , Lin Chun-Teng , Chang Yu-Jun , Lin Ying-Ju , Liang Wen-Miin , Lin Jeff Chien-Fu
Published: May 2021

Background

Most unstable trochanteric fractures are treated with internal fixation and often with high complication rates. Hemiarthroplasty might be an alternative method in difficult condition, especially in unstable comminuted fracture in fragile bone. However, few have investigated the long-term outcomes after hemiarthroplasty for unstable trochanteric fracture. We conducted a population-based retrospective cohort study of trochanteric fracture after primary hemiarthroplasty using competing risk analysis on their long-term outcomes, including mortality, readmission and reoperation.

Methods

We studied a total of 2798 patients over 60 years old, with a mean age of 79 years, of which 68% are females and 67.23% have at least one comorbidity. They underwent a hemiarthroplasty for unstable trochanteric fracture during the period between January 1, 2000 and December 31, 2010 and were follow-up until the end of 2012, or death. Survival analysis and Cox model were used to characterize mortality. Competing risk analysis and Fine and Gray model were used to estimate the cumulative incidences of the first readmission and the first reoperation.

Results

The follow-up mortality rate for 1-year was 17.94%; 2-year, 29.76%; 5-year, 56.8%; and 10-year, 83.38%. The cumulative incidence of the first readmission was 16.4% for 1-year and 22.44% for 3-year. The cumulative incidence of the first reoperation was 13.87% for 1-year, 18.11% for 2-year, 25.79% for 5-year, and 38.24% for 10-year. Male gender, older age, higher Charlson Comorbidity Index (CCI) and lower insured amount were all risk factors for the overall mortality. Older age and higher CCI were risk factors for the first readmission. Older age was a protective factor for reoperation, which is likely due to the competing death.

Conclusions

The mortality and revision rates after hemiarthroplasty for unstable trochanteric fracture are acceptable as a salvage procedure for this fragile sub-population.
Despite higher revision rate, MoM large-head THA offers better clinical scores than HR: 14-year results from a randomized controlled trial involving 48 patients
Authors: Kostretzis Lazaros , Lavigne Martin , Kiss Marc-Olivier , Shahin Maged , Barry Janie , Vendittoli Pascal-André
Published: May 2021

Background

The high failure rates of metal on metal (MoM) large diameter head total hip arthroplasty (LDH THA) and hip resurfacing (HR) prevented their long-term comparisons with regards to clinical outcome. Such knowledge would be important as ceramic LDH bearing is now available. With long-term follow-up, we investigated the difference in 1) patient-reported outcome measures (PROMs); 2) revision and adverse events rates, and 3) metal ion levels between MoM LDH THA and HR.

Methods

Forty-eight patients were randomized for LDH THA (24) or HR (24) with the same MoM articulation. At a mean follow-up of 14 years, we compared between groups different PROMs, the number of revisions and adverse events, whole blood Cobalt (Co) and Chromium (Cr) ion levels, and radiographic signs of implant dysfunction.

Results

LDH THA (all cases: revised and well-functioning) had significantly better WOMAC (94 versus 85, p = 0.04), and more frequently reported having no limitation (p = 0.04). LDH THA revision rate was 20.8% (5/24) versus 8.3% (2/24) for HR (p = 0.4). Mean Co and Cr ion levels were higher in LDH THA compared to the HR (Co: 3.8 μg/L vs 1.7 μg/L; p = 0.04 and Cr: 1.9 μg/L vs 1.4 μg/L, p = 0.1). On radiographic analyses, 2 LDH THAs showed signs of adverse reaction to metal debris, whereas 1 loose femoral HR component was documented.

Conclusion

In the long-term, MoM LDH THA had a high trunnion related revision rate but nonetheless showed better PROMs compared to HR. Provided with a well-functioning modular junction, non-MoM LDH THA would offer an appealing option.

Trial registration

ClinicalTrials.gov (NCT04516239), August 18, 2020. Retrospectively registered.
Preperitoneal herniation as a complication of tansabdominal preperitoneal patch plasty: a report of two cases
Authors: Zou Zhenyu , Zhu Yilin , Wang Fan , Cao Jinxin , Liu Yuchen , Yang Huiqi , Wang Minggang
Published: May 2021

Background

Preperitoneal herniation is a rare complication after transabdominal preperitoneal patch plasty (TAPP) and may be caused by inadequate peritoneal closure. We herein report two cases of postoperative small bowel obstruction due to preperitoneal herniation through a disrupted peritoneum.

Case presentation

Two men in their 70s were admitted to our center because of small bowel obstruction after TAPP. After examinations and unsuccessful conservative treatment, emergency laparoscopic exploration was performed. Preperitoneal herniation through the disrupted peritoneum was found. The herniated small bowel was reduced and the peritoneum was properly reclosed. The patients recovered and were discharged with normal bowel function.

Conclusions

Inadequate peritoneal closure may cause preperitoneal herniation and lead to postoperative small bowel obstruction and even death. Hernia surgeons can avoid this complication by improving their suture technique and paying attention to the procedure details.
A case report of cervicothoracic penetrating injury with retention of foreign body
Authors: Hui Yang , Yang Xinxin , Ma Dengdian , Yao Mengwei , Liu Xinying , Dai Yunbing , Huang Qinyuan , Liu Tao , Xu Jing , Li Xiaoyu
Published: May 2021

Background

Cervicothoracic penetrating injury, considered to be relatively rare, has a complicated mechanism that is difficult to treat. In this report, a special case of cervicothoracic injury caused by foreign body penetration was elucidated. In this case, the injury location and the involved foreign body were exceptionally particular, which induced a challenging process of diagnosis and treatment.

Case presentation

A male patient suffered from a serious injury caused by a thick branch that pierced through his neck in a traffic accident between an electric car and a tricycle carrying wood. There were also local injuries in the left scapular region. After an emergency multidisciplinary consultation, the patient was diagnosed and subsequently treated with vascular exploration and repair (common carotid artery), intrathoracic foreign body extraction, chest exploration, debridement, and suture. After surgery, he was transferred to the emergency intensive care unit for anticoagulation and anti-infection treatment. Finally, after the improvement of his physical condition, the patient was transferred to the general ward for further treatment and was successfully discharged from the hospital. Once discharged, the patient lived a normal life, free from sequelae or complications.

Conclusion

It may be an extremely daunting task to cure cervicothoracic penetrating injury due to its rare occurrence in clinical practice. Different from the previous cervicothoracic traumas, the injury location in this case is exceedingly particular. In general, the common cervicothoracic trauma is associated with damage to the trachea, esophagus, throat, and other structures, easily resulting in dyspnea, which, however, does not occur in this case. The insertion position of foreign body is exceptionally particular as it does not pierce the common carotid artery but poses compression on it, which induces ischemia. It is essential for the successful treatment that the treatment plan is formulated via the detailed imaging examination and careful multidisciplinary consultation.
Rational design and structure-based engineering of alkaline pectate lyase from Paenibacillus sp. 0602 to improve thermostability
Authors: Zhou Zhanping , Wang Xiao
Published: May 2021

Background

Ramie degumming is often carried out at high temperatures; therefore, thermostable alkaline pectate lyase (PL) is beneficial for ramie degumming for industrial applications. Thermostable PLs are usually obtained by exploring new enzymes or reconstructing existing enzyme by rational design. Here, we improved the thermostability of an alkaline pectate lyase (PelN) fromPaenibacillussp. 0602 with rational design and structure-based engineering.

Results

From 26 mutants, two mutants of G241A and G241V showed a higher thermostability compared with the wild-type PL. The mutant K93I showed increasing specific activity at 45 °C. Subsequently, we obtained combinational mutations (K93I/G241A) and found that their thermostability and specific activity improved simultaneously. The K93I/G241A mutant showed a half-life time of 15.9 min longer at 60 °C and a melting temperature of 1.6 °C higher than those of the wild PL. The optimum temperature decreased remarkably from 67.5 °C to 60 °C, accompanied by a 57% decrease inKmcompared with theKmvalue of the wild-type strain. Finally, we found that the intramolecular interaction in PelN was the source in the improvements of molecular properties by comparing the model structures. Rational design of PelN was performed by stabilizing the α-helices with high conservation and increasing the stability of the overall structure of the protein. Two engineering strategies were applied by decreasing the mutation energy calculated by Discovery Studio and predicting the free energy in the process of protein folding by the PoPMuSiC algorithm.

Conclusions

The results demonstrated that the K93I/G241A mutant was more suitable for industrial production than the wild-type enzyme. Furthermore, the two forementioned strategies could be extended to reveal engineering of other kinds of industrial enzymes.
Apoplexy of Crooke cell tumour leading to the diagnosis of severe Cushing disease; a case report
Authors: de Silva Nipun Lakshitha , Somasundaram Noel , Constantine Roshana , Kularatna Himashi
Published: May 2021

Background

Patients with Crooke cell tumours present with features of Cushing syndrome or mass effect. There are few reports of patients with Crooke cell tumours presenting due to apoplexy. All of them had silent tumours. Patients with Cushing syndrome caused by Crooke cell tumours have not been reported to present with apoplexy.

Case presentation

A 35-year-old female presented with sudden onset headache and visual loss for 1 week. She had secondary amenorrhoea for 10 years. There were features of Cushing syndrome including central obesity, multiple monomorphic acne, dorso-cervical and supraclavicular fat pads, hypertension, proximal weakness, pigmentation and refractory hypokalaemia. She was found to have markedly elevated serum cortisol, central hypothyroidism and hypogonadotropic hypogonadism. There was a mass in the sellar region (4.7 cm × 1.9 cm × 5.3 cm) suggestive of a pituitary tumour extending to the suprasellar region. Imaging showed evidence of bleeding and compression of the optic chiasm. She underwent urgent trans-sphenoidal excision of the tumour. Histology was compatible with a pituitary neuroendocrine tumour. There was margination of ACTH reactivity to the cell periphery and ring like positivity in most of the cells in the cytokeratin stain. Features were in favour of a Crooke cell tumour. After surgery she improved gradually and became eucortisolaemic.

Conclusions

This is a unique presentation of an apoplexy of Crooke cell tumour causing Cushing syndrome. Delayed health seeking behaviour of this patient despite severe Cushing disease could have led to this presentation which has not been reported before.
Salivary Porphyromonas gingivalis predicts outcome in oral squamous cell carcinomas: a cohort study
Authors: Chen Qingli , Shao Zhe , Liu Ke , Zhou Xiaocheng , Wang Lin , Jiang Erhui , Luo Tingting , Shang Zhengjun
Published: May 2021

Background

Studies suggest Porphyromonas gingivalis (Pg) increased the incidence of oral squamous cell carcinoma (OSCC). However, fimA genotypes distribution of Pg, the origination of Pg in tissue, and its prognostic value are inconclusive. We aimed to investigate the frequency of fimA genotypes in OSCC patients, study the association between Pg and OSCC, and explore the prognostic value of Pg.

Methods

The abundance of Pg in saliva from the OSCC group and the OSCC-free group was analysed by qPCR. The presence of Pg was explored in OSCC tissue and para-cancerous tissue by in situ hybridization. The frequency of fimA genotypes in saliva and OSCC tissue was determined by PCR, then PCR products were sequenced and compared. Clinical data were extracted, and patients followed up for a median period of 23 months. Clinicopathological variables were compared with the abundance of Pg using Pearson Chi-square test or Fisher’s exact test. The disease-free survival (DFS) rate was calculated by Kaplan–Meier method with log-rank tests.

Results

Comparing the OSCC-free group, 95 patients with OSCC showed a high abundance of Pg in saliva (P = 0.033), and OSCC tissue showed strong in situ expression of Pg compared with paired normal tissue. Patients with OSCC showed a dominant distribution of Pg with genotype I + Ib (21.1%), II (31.6%), and IV (21.1%). FimA genotypes detected in saliva were in accordance with those in OSCC tissue, there was, moreover, a significant similarity in amplified Pg fragments. Of the 94 responsive OSCC patients, the recurrence rate was 26.6% (25/94). Overabundance of Pg in saliva showed advanced pathologic staging (P = 0.008), longer disease-free time (P = 0.029) and lower recurrence rate (P = 0.033). The overabundance of Pg in saliva was associated with improved disease-free survival (P = 0.049).

Conclusions

This study indicated that Pg might involve in the pathogenesis of OSCC, Pg carrying fimA I, Ib, II, and IV were prevalent genotypes in patients with OSCC, the provenance of Pg in OSCC tissue might be from the salivary microbial reservoir, and the abundance of Pg in saliva might consider as a favorable potential prognostic indicator in OSCC.
Presence of voids after three obturation techniques in band‐shaped isthmuses: a micro‐computed tomography study
Authors: Zhang Pengfei , Yuan Keyong , Jin Qiaoqiao , Zhao Fen , Huang Zhengwei
Published: May 2021

Background

The objective of the present micro-computed tomography (micro-CT) study was to assess the presence of voids in band-shaped isthmuses obturated using three different filling techniques.

Methods

Twenty-four artificial molar teeth with a band-shaped isthmus were allocated to three groups (n = 8) for obturation, according to the filling technique: single-cone (SC), continuous wave of condensation (CWC) or lateral condensation (LC). Obturation was performed with gutta-percha (GP) cones and iRoot SP (Innovative Bioceramix, Vancouver, Canada). Post-filling micro-CT scanning was performed. The percentage of filling materials and void volumes were calculated in the isthmus areas and data were analyzed using one-way ANOVA and Tukey tests.

Results

The mean percentage of void volumes and corresponding filling percentages in the isthmus areas after obturation in the SC groups was 22.98 % ± 1.19 %, 77.02 % ± 1.19 %; in the CWC groups 10.46 % ± 2.28 %, 89.54 % ± 2.28 %; and in the LC groups was 13.14 % ± 1.85 %, 86.86 % ± 1.85 %, respectively.

Conclusions

In band-shaped isthmus area, the obturation quality of CWC was superior to SC and LC techniques.
Impact of endodontic case difficulty on operating time of single visit nonsurgical endodontic treatment under general anesthesia
Authors: Chung Shin Hye , Chang Juhea
Published: May 2021

Background

A Case Difficulty Assessment Form was designed for use in endodontic curricula, and to assist practitioners with treatment planning, referral and recording. The aim of this study was to determine how endodontic case difficulty factors influence the operating time of single-visit nonsurgical endodontic treatments under general anesthesia.

Methods

Data on 198 single-visit endodontic treatments (80 anterior teeth, 43 premolars, and 75 molars) performed under general anesthesia by a specialized practitioner were obtained from 119 special needs patients (mean [SD] age = 30.7 [14.7] years). Total duration of operation was analyzed with relation to demographic and dental factors and American Association of Endodontists (AAE) Case Difficulty Assessment factors. Mann–Whitney U test, t-test, and Kruskal–Wallis test were used to assess relationships between operating time and confounding factors (p < 0.05).

Results

High difficulty cases required significantly longer time to complete operations than treatments of minimal-to-moderate difficulty regardless of tooth type (p < 0.05). Demographic factors of the patients rarely influenced operating time length. Among variables included in the AAE Case Difficulty Assessment Form, tooth position, crown morphology, root morphology, canal appearance, and periodontal condition were significantly associated with increased operating time (p < 0.05).

Conclusions

A higher level of case difficulty contributed to increased duration of endodontic treatment under general anesthesia indicating that Endodontic Case Difficulty Assessment Form is useful for predicting the duration of nonsurgical endodontic treatment. Among many factors, complicated anatomic features of the treated teeth increased case complexity and extended operating time.
Assessing health disparities in breast cancer incidence burden in Tennessee: geospatial analysis
Authors: Salmeron Bonita , Mamudu Lohuwa , Liu Xiaohui , Whiteside Martin , Williams Faustine
Published: May 2021

Background

Tennessee women experience the 12th highest breast cancer mortality in the United States. We examined the geographic differences in breast cancer incidence in Tennessee between Appalachian and non-Appalachian counties from 2005 to 2015.

Methods

We used ArcGIS 10.7 geospatial analysis and logistic regression on the Tennessee Cancer Registry incidence data for adult women aged ≥ 18 years (N = 59,287) who were diagnosed with breast cancer from 2005 to 2015 to evaluate distribution patterns by Appalachian county designation. The Tennessee Cancer Registry is a population-based, central cancer registry serving the citizens of Tennessee and was established by Tennessee law to collect and monitor cancer incidence. The main outcome was breast cancer stage at diagnosis. Independent variables were age, race, marital status, type of health insurance, and county of residence.

Results

Majority of the sample were White (85.5%), married (58.6%), aged ≥ 70 (31.3%) and diagnosed with an early stage breast cancer (69.6%). More than half of the women had public health insurance (54.2%), followed by private health insurance coverage (44.4%). Over half of the women resided in non-Appalachian counties, whereas 47.6% were in the Appalachian counties. We observed a significant association among breast cancer patients with respect to marital status and type of health insurance coverage (p =  < 0.0001). While the logistic regression did not show a significant result between county of residence and breast cancer incidence, the spatial analysis revealed geographic differences between Appalachian and non-Appalachian counties. The highest incidence rates of 997.49–1164.59/100,000 were reported in 6 Appalachian counties (Anderson, Blount, Knox, Rhea, Roane, and Van Buren) compared to 3 non-Appalachian counties (Fayette, Marshall, and Williamson).

Conclusions

There is a need to expand resources in Appalachian Tennessee to enhance breast cancer screening and early detection. Using geospatial techniques can further elucidate disparities that may be overlooked in conventional linear analyses to improve women’s cancer health and associated outcomes.
The myeloid sarcoma treated by Venetoclax with hypomethylating agent followed by stem cell transplantation: rare case report
Authors: Shatilova Aleksina , Girshova Larisa , Zaytsev Daniil , Budaeva Irina , Mirolyubova Yuliya , Ryzhkova Darya , Grozov Roman , Bogdanov Konstantin , Nikulina Tatiana , Motorin Dmitriy , Zammoeva Darina , Efremova Svetlana , Ivanov Vladimir , Petukhov Alexey , Alekseeva Yuliya , Zaritskey Andrey
Published: May 2021

Background

Myeloid sarcoma (MS) is a very rare condition, develops both in patients with other hematological neoplasms, and as isolated tumor. MS of the gynecologic tract is extremely rare. An available literature data about diagnosis and management of MS is summarized in the article. The role of chemotherapy, radiation therapy, surgery and bone marrow transplantation in the treatment is discussed. Polychemotherapy and allogeneic bone marrow transplantation were suggested to be the optimal treatment strategy of MS of the gynecological tract. The use of new targeted agents results in promising clinical data.

Case presentation

We are presenting a rare clinical case of a MS of the uterine cervix with concomitant bone marrow involvement and describe all the peculiarities of the clinical course, diagnosis, and treatment. The patient received chemotherapy followed by allogeneic bone marrow transplantation. The pre-transplant therapy allowed us to perform allogeneic bone marrow transplantation with the deepest response possible: complete PET-negative and MRD-negative remission of the disease.

Conclusions

MS remains a subject of discussion regarding its diagnostic and therapeutic aspects. The use of novel targeting agents can be perspective option for patient with extramedullary disease.
A mechanistic study on the inhibition of bacterial growth and inflammation by Nerium oleander extract with comprehensive in vivo safety profile
Authors: Shafiq Yousra , Naqvi Syed Baqir Shyum , Rizwani Ghazala H. , Asghar Muhammad Arif , Bushra Rabia , Ghayas Sana , Rehman Ahad Abdul , Asghar Muhammad Asif
Published: May 2021

Background

Nerium oleander (L.) is well known traditionally used medicinal plant with several pharmacological activities. However, the anti-bacterial, anti-inflammatory activity and in vivo toxicity potential of floral parts of this plant are not reported. Therefore the present study was designed to investigate these activities of Nerium oleander ethanolic flower extract (NOEE) in different animal models.

Methods

Antimicrobial activity of plant extract was compared with five different antibiotics using the disk diffusion method. The time-killing kinetic assay and bacterial killing mechanism of NOEE were also performed. Anti-inflammatory activity was assessed using granuloma induced by cotton-pellet, rat paw edema induced by carrageenan and levels of different inflammatory biomarkers on healthy Wistar rats. The protein and mRNA expressions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also measured. Acute (14 days) and sub-acute (28 days) oral toxicity studies were also performed on healthy Sprague Dawley rats.

Results

NOEE produced highly significant (P < 0.005) and significant (P < 0.05) zones of inhibition at 30 mg/mL and 20 mg/mL respectively against most of the tested bacterial strains. NOEE produced a more drop in viable counts of Gram-negative isolates within 20 min. After 12 h exposure with NOEE, the SEM images of MRSA showed the destruction of cell membrane. NOEE showed highly significant (P < 0.005) anti-inflammatory activity in cotton-pellet and carrageenan inflammatory models. In addition, treatment with NOEE also decreased the production of NO, PGE2, TNF-α and IL-1β in the rat paw after treated with carrageenan. Similarly, NOEE also suppressed the inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, and cyclooxygenase-2 (COX-2) mRNA expressions. It is also showed highly significant reduction in total leukocyte count (73.09%) and C-reactive protein levels (54.60%). NOEE also inhibited COX-1, COX-2, 5-LO and 12-LO in a highly significant manner. Moreover, acute and sub-acute toxicity studies of NOEE in rats confirm the toxicity with hepatotoxicity at higher doses (2000 mg/kg) i.e. four times greater than the therapeutic dose.

Conclusion

It is concluded that crude flower extract of N. oleander is a potent antimicrobial and anti-inflammatory agent with no toxicity potential at therapeutic doses.
Knowledge of breast cancer among medical students in Syrian Private University, Syria: a cross-sectional study
Authors: Ismail Hlma , Shibani Mosa , Zahrawi Hanaa Wael , Slitin Ali Fouad , Alzabibi Mhd Amin , Mohsen Fatema , Armashi Humam , Bakr Aliaa , Turkmani Khaled , Sawaf Bisher
Published: May 2021

Background

Breast cancer is the most common cancer among women and the second leading cause of cancer death globally. Since early diagnosis is crucial to reducing mortality, high levels of knowledge regarding general information, risk factors, and symptoms are required among healthcare professionals to deliver breast cancer care. This study aimed to determine Syrian medical students’ knowledge about breast cancer in the fields of general knowledge, common clinical features, and risk factors.

Methods

This cross-sectional study was conducted at the Syrian Private University in October 2019 (Breast Cancer Awareness Month), Damascus, during the Syrian war crisis. Data were collected through self-administered surveys and analyzed using the Statistical Package for Social Sciences version 25.0 (SPSS Inc., United States). The chi-square test was applied to assess the relationship between the level of knowledge and gender. One way analysis of variance was performed to assess the overall differences in mean knowledge score by study year, GPA, mother’s education, and source of information. Unpaired Student’s T-test was used to analyze the differences in mean knowledge scores (continuous variable) based on smoking status and alcohol consumption.

Results

Of 320 students, 301 completed the questionnaire (response rate = 94.0%), of which 179(59.5%) were males. The study revealed above-average knowledge scores (total mean = 68.4%) regarding breast cancer, general information (71.9%), common clinical features (71.6%), and risk factors (71.6%). Clinical students (4th, 5th, and 6th years) scored higher compared with pre-clinical students (1st, 2nd, and 3rd years).

Conclusion

This study showed above-average knowledge scores regarding breast cancer. More efforts to correct misinformation, through reassessing the university curriculum and promoting awareness about breast cancer are required.
Exploring wellbeing in first year medical students amidst a curriculum change
Authors: Merrick Deborah , Mbaki Yvonne , Pratten Margaret K. , Simpson Timothy G.
Published: May 2021

Background

The support of student wellbeing features highly in all higher education institutional agendas. For medical students good physical and mental health can help prevent burnout, equip students for their future healthcare setting and indirectly improve patient care. At the University of Nottingham (UK), we were keen to explore undergraduate medical students perceived wellbeing before, during, and after an early years’ (years 1-3) curriculum change. A restructure of the curriculum enabled personal wellbeing sessions to be embedded and directly linked to the pastoral support system.

Methods

Students’ perceived wellbeing was assessed through a questionnaire distributed to three cohorts of first year students at the start and end of the autumn semester.

Results

The data showed a clear improvement of perceived physical health at the end of the first semester following the curriculum change, alongside increased mood and ability to relax. A surprising outcome of this study was that students reported increased stress levels at the end of the semester, which we believe may be attributed to the change in assessment within the new curriculum. Our medical students are now facing end of year summative examinations, but are acutely aware of their progress as they undertake frequent formative assessments during the year. We propose that comparison of performance with peers is having a direct impact on perceived stress in these cohorts.

Conclusions

The study has shown that embedding wellbeing in the curriculum can have positive effects even within a changing curriculum. The importance of evolving wellbeing provision and support based on the needs of the student population is essential and probably never more in need than at this moment in time.
A comparison of orthopaedic surgery and internal medicine perceptions of USMLE Step 1 pass/fail scoring
Authors: Mun Frederick , Scott Alyssa R. , Cui David , Lehman Erik B. , Jeong Seongho , Chisty Alia , Juliano Paul J. , Hennrikus William L. , Hennrikus Eileen F.
Published: May 2021

Background

United States Medical Licensing Examination Step 1 will transition from numeric grading to pass/fail, sometime after January 2022. The aim of this study was to compare how program directors in orthopaedics and internal medicine perceive a pass/fail Step 1 will impact the residency application process.

Methods

A 27-item survey was distributed through REDCap to 161 U.S. orthopaedic residency program directors and 548 U.S. internal medicine residency program directors. Program director emails were obtained from the American Medical Association’s Fellowship and Residency Electronic Interactive Database.

Results

We received 58 (36.0%) orthopaedic and 125 (22.8%) internal medicine program director responses. The majority of both groups disagree with the change to pass/fail, and felt that the decision was not transparent. Both groups believe that the Step 2 Clinical Knowledge exam and clerkship grades will take on more importance. Compared to internal medicine PDs, orthopaedic PDs were significantly more likely to emphasize research, letters of recommendation from known faculty, Alpha Omega Alpha membership, leadership/extracurricular activities, audition elective rotations, and personal knowledge of the applicant. Both groups believe that allopathic students from less prestigious medical schools, osteopathic students, and international medical graduates will be disadvantaged. Orthopaedic and internal medicine program directors agree that medical schools should adopt a graded pre-clinical curriculum, and that there should be a cap on the number of residency applications a student can submit.

Conclusion

Orthopaedic and internal medicine program directors disagree with the change of Step 1 to pass/fail. They also believe that this transition will make the match process more difficult, and disadvantage students from less highly-regarded medical schools. Both groups will rely more heavily on the Step 2 clinical knowledge exam score, but orthopaedics will place more importance on research, letters of recommendation, Alpha Omega Alpha membership, leadership/extracurricular activities, personal knowledge of the applicant, and audition electives.
Normative framework of informed consent in clinical research in Germany, Poland, and Russia
Authors: Orzechowski Marcin , Woniak Katarzyna , Timmermann Cristian , Steger Florian
Published: May 2021

Background

Biomedical research nowadays is increasingly carried out in multinational and multicenter settings. Due to disparate national regulations on various ethical aspects, such as informed consent, there is the risk of ethical compromises when involving human subjects in research. Although the Declaration of Helsinki is the point of reference for ethical conduct of research on humans, national normative requirements may diverge from its provisions. The aim of this research is to examine requirements on informed consent in biomedical research in Germany, Poland, and Russia to determine how each national regulatory framework relates to the provisions of the Declaration of Helsinki.

Methods

For this analysis, we conducted a search of the legal databases “Gesetze im Internet” for Germany, “Internetowy System Aktow Prawnych” for Poland, and “ГAPAHT – Garant” for Russia. The search was complemented by a review of secondary literature contained in the databases Google Scholar, PubMed, Polish National Library, and eLibrary.ru. We have identified 21 normative regulations containing provisions on informed consent in clinical research in all three countries. The content of these documents was systematically categorized and analyzed.

Results

The normative framework in all three countries shows a strong commitment towards the core ethical principles of research envisaged in the Declaration of Helsinki. Nevertheless, provisions on informed consent vary between these three countries. The differences range from the method and language in which information should be provided, through the amount of information required to be disclosed, to the form of documenting consent or withdrawal. In the case of research on vulnerable groups, these differences are particularly visible.

Conclusions

The identified differences can negatively impact the ethical conduct of international clinical studies. Attention needs to be paid that flexibilities within national regulations are not misused to undermine the protection of research subjects. Achieving global or regional legislative harmonization might prove impossible. Such lack of legal consensus reinforces the significance of the international ethical agreements.

Trial registration: Not applicable.
Identification of hot regions in hub protein–protein interactions by clustering and PPRA optimization
Authors: Lin Xiaoli , Zhang Xiaolong
Published: May 2021

Background

Protein–protein interactions (PPIs) are the core of protein function, which provide an effective means to understand the function at cell level. Identification of PPIs is the crucial foundation of predicting drug-target interactions. Although traditional biological experiments of identifying PPIs are becoming available, these experiments remain to be extremely time-consuming and expensive. Therefore, various computational models have been introduced to identify PPIs. In protein-protein interaction network (PPIN), Hub protein, as a highly connected node, can coordinate PPIs and play biological functions. Detecting hot regions on Hub protein interaction interfaces is an issue worthy of discussing.

Methods

Two clustering methods, LCSD and RCNOIK are used to detect the hot regions on Hub protein interaction interfaces in this paper. In order to improve the efficiency of K-means clustering algorithm, the best k value is selected by calculating the distance square sum and the average silhouette coefficients. Then, the optimization of residue coordination number strategy is used to calculate the average coordination number. In addition, the pair potentials and relative ASA (PPRA) strategy is also used to optimize the predicted results.

Results

DataHub dataset and PartyHub dataset were used to train two clustering models respectively. Experiments show that LCSD and RCNOIK have the same coverage with Hub protein datasets, and RCNOIK is slightly higher than LCSD in Precision. The predicted hot regions are closer to the standard hot regions.

Conclusions

This paper optimizes two clustering methods based on PPRA strategy. Compared our methods for hot regions prediction against the well-known approaches, our improved methods have the higher reliability and are effective for predicting hot regions on Hub protein interaction interfaces.
Reducing unmet need for contraceptive services among youth in Homabay and Narok counties, Kenya: the role of community health volunteers – a qualitative study
Authors: Ormel Hermen , Oele George , Kok Maryse , Oruko Happiness , Oluoch Beatrice , Smet Eefje , Indalo Dorcus
Published: May 2021

Background

Access to contraceptive services is a cornerstone of human well-being. While Community Health Volunteers (CHVs) promote family planning in Kenya, the unmet need for contraceptives among youth remains high. CHVs seem to pay little specific attention to the contraceptive needs of the youth.

Methods

We conducted a qualitative study exploring the role of CHVs in increasing access and uptake of contraceptive services among youth aged 18–24 years in Narok and Homabay Counties, Kenya. We undertook 37 interviews and 15 focus group discussions involving CHVs, youth, community members, community leaders, youth leaders and health programme managers. Data were recorded, transcribed, translated, coded and thematically analysed, according to a framework that included community, CHV and health system-related factors.

Results

CHVs often operated in traditional contexts that challenge contraceptive use among unmarried female and male youth and young married couples. Yet many CHVs seemed to have overcome this potential ‘barrier’ as well as reigning misconceptions about contraceptives. While private and facility-based public contraceptive services were somehow available, CHVs were the preferred service provider for many youth due to ease of access and saving time and transport costs. This was influenced by varied perceptions among youth of CHVs’ knowledge, skills and attitudes regarding contraceptives and provider-client interaction, and specifically their commitment to maintain confidentiality.

Conclusions

CHVs have the potential to increase access to contraceptives for young people, reducing unmet need for contraceptives. Their knowledge, skills and attitudes need strengthening through training and supervision, while incentives to motivate them and broadening the range of contraceptives they are allowed to offer should be considered.
Attitude toward dementia and preferences for diagnosis in Japanese health service consumers
Authors: Oba Hikaru , Matsuoka Teruyuki , Kato Yuka , Watson Rochelle , Mansfield Elise , Sanson-Fisher Rob , Narumoto Jin
Published: May 2021

Background

Being diagnosed with dementia is a confronting experience for any individual and their caregiver. However, a diagnosis provides opportunity for future preparation for management of the condition. This study investigated attitudes toward dementia and preferences for diagnosis among a sample of health service consumers in Japan.

Methods

Participants were patients or accompanying support persons (n = 217) who visited the specialty outpatient clinic of four hospital departments. The survey was conducted using an iPad with answers sent automatically to a secure server. The survey included items about the participants’ most feared diseases and the reasons behind those fears, estimates of dementia prevalence in Japan, and preferences regarding a diagnosis of dementia and the reasons for their preference.

Results

The most feared disease was cancer (43.8 %), followed by dementia (18 %). Those selecting dementia most commonly reported practical, emotional and social impacts as the reasons why they most feared this condition. Almost all participants preferred to know the diagnosis of dementia as soon as possible for themselves, with significantly fewer preferring their spouse to know as soon as possible if they had dementia (95.9 % for self vs. 67.5 % for partner/spouse, p < 0.001). On average, participants estimated that 18.1 % of Japanese people are diagnosed with dementia by age 65, while they thought that 43.7 % of Japanese people are diagnosed with dementia by age 85.

Conclusions

The findings highlight a need for community education about the significant impacts of dementia on the lives of individuals and their caregivers. People were more reluctant for their spouse to receive a diagnosis as soon as possible if they had dementia. Physicians should sensitively disclose diagnosis and ensure they involve both the patient and their relatives in discussions about diagnosis disclosure.
Ancestry specific associations of a genetic risk score, dietary patterns and metabolic syndrome: a longitudinal ARIC study
Authors: Hardy Dale S. , Racette Susan B. , Garvin Jane T. , Gebrekristos Hirut T. , Mersha Tesfaye B.
Published: May 2021

Background

Associations have been observed among genetic variants, dietary patterns, and metabolic syndrome (MetS). A gap in knowledge is whether a genetic risk score (GRS) and dietary patterns interact to increase MetS risk among African Americans. We investigated whether MetS risk was influenced by interaction between a GRS and dietary patterns among Whites and African Americans. A secondary aim examined if molecular genetic clusterings differed by racial ancestry.

Methods

We used longitudinal data over 4-visits (1987–1998) that included 10,681 participants aged 45–64y at baseline from the Atherosclerosis Risk in Communities study (8451 Whites and 2230 African Americans). We constructed a simple-count GRS as the linear weighted sum of high-risk alleles (0, 1, 2) from cardiovascular disease polymorphisms from the genome-wide association studies catalog associated with MetS risk. Three dietary patterns were determined by factor analysis of food frequency questionnaire data: Western, healthy, and high-fat dairy. MetS was defined according to the 2016 National Cholesterol Education Program Adult Treatment Panel III criteria but used 2017 American Heart Association/American College of Cardiology criteria for elevated blood pressure. Analyses included generalized linear model risk ratios (RR), 95% confidence intervals (CI), and Bonferroni correction for multiple testing.

Results

The Western dietary pattern was associated with higher risk for MetS across increasing GRS tertiles among Whites (p < 0.017). The high-fat dairy pattern was protective against MetS, but its impact was most effective in the lowest GRS tertile in Whites (RR = 0.62; CI: 0.52–0.74) and African Americans (RR = 0.67; CI: 0.49–0.91). Among each racial group within GRS tertiles, the Western dietary pattern was associated with development and cycling of MetS status between visits, and the high-fat dairy pattern with being free from MetS (p < 0.017). The healthy dietary pattern was associated with higher risk of MetS among African Americans which may be explained by higher sucrose intake (p < 0.0001). Fewer genes, but more metabolic pathways for obesity, body fat distribution, and lipid and carbohydrate metabolism were identified in African Americans than Whites. Some polymorphisms were linked to the Western and high-fat dairy patterns.

Conclusion

The influence of dietary patterns on MetS risk appears to differ by genetic predisposition and racial ancestry.
Surface display as a functional screening platform for detecting enzymes active on PET
Authors: Heyde Sophia A. H. , Arnling Bååth Jenny , Westh Peter , Nørholm Morten H. H. , Jensen Kenneth
Published: May 2021

Poly(ethylene terephthalate) (PET) is the world’s most abundant polyester plastic, and its ongoing accumulation in nature is causing a global environmental problem. Currently, the main recycling processes utilize thermomechanical or chemical means, resulting in the deterioration of the mechanical properties of PET. Consequently, polluting de novo synthesis remains preferred, creating the need for more efficient and bio-sustainable ways to hydrolyze the polymer. Recently, a PETase enzyme from the bacterium Ideonella sakaiensis was shown to facilitate PET biodegradation, albeit at slow rate. Engineering of more efficient PETases is required for industrial relevance, but progress is currently hampered by the dependency on intracellular expression in Escherichia coli. To create a more efficient screening platform in E. coli, we explore different surface display anchors for fast and easy assaying of PETase activity. We show that PETases can be functionally displayed on the bacterial cell surface, enabling screening of enzyme activity on PET microparticles – both while anchored to the cell and following solubilization of the enzymes.
Inhibition of KIF20A by transcription factor IRF6 affects the progression of renal clear cell carcinoma
Authors: Ma Xinwei , Wang Xiaoqi , Dong Qian , Pang Hongquan , Xu Jianming , Shen Junkang , Zhu Jianbing
Published: May 2021

Background

Renal clear cell carcinoma (ccRCC) is one of the most common malignant tumors, whose incidence is increasing year by year. IRF6 plays an important role in the occurrence of tumors, although there is yet no report on its expression in ccRCC.

Methods

The expression of IRF6 and KIF20A in ccRCC was predicted by GEPIA and HAP databases. In addition, GEPIA database predicted the relationship between IRF6 and KIF20A expressions and the pathological staging, overall survival, and disease-free survival of ccRCC. The possible binding sites of IRF6 and KIF20A promoters were predicted by JASPAR database and verified by luciferase and ChIP assays. The specific effects of IRF6 on ccRCC cell proliferation, invasion and apoptosis were subsequently examined at both cellular level and animal level.

Results

The database predicted down-regulated IRF6 expression in renal carcinoma tissues and its correlation with poor prognosis. IRF6 overexpression inhibited cRCC cell proliferation, invasion and migration. In addition, up-regulated KIF20A expression in renal carcinoma tissues and its association with prognosis were also predicted. Interference with KIF20A inhibited the proliferation, invasion, and migration of ccRCC cells. Finally, we confirmed that KIF20A is a functional target of IRF6 and can partially reverse the effects of IRF6 on the proliferation, invasion and migration of ccRCC cells. Conclusion: Inhibition of KIF20A by transcription factor IRF6 affects cell proliferation, invasion and migration in renal clear cell carcinoma.