bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between homocysteine levels and cardiovascular disease risk among middle-aged and elderly adults in Taiwan
Authors: Shih Chin-Chuan , Shih Yu-Lin , Chen Jau-Yuan
Published: April 2021

Background

Our study aimed to determine the association between homocysteine levels and cardiovascular disease (CVD) risk in middle-aged and elderly adults in a community in northern Taiwan.

Methods

Participants in our study included adults aged 50 to 85 years old during community health examinations in 2019. A total of 396 people were enrolled, the ethnicity of all participants is Chinese. We divided participants according to tertiles of ln[homocysteine] level (low, middle and high groups). The CVD risk was calculated by the Framingham cardiovascular risk score (FRS). An FRS ≥ 20% indicated high CVD risk. Pearson correlation coefficients were calculated between homocysteine level and other cardio-metabolic risk factors while adjusting for age. Multivariate logistic regression analysis was used to determine the association of high and middle ln[homocysteine] groups with high CVD risk after adjusting age, sex, uric acid, creatinine, and body mass index (BMI). The Youden index and receiver operating characteristic (ROC) curves were performed to determine the optimized cut-off value.

Results

There were 396 people enrolled for analysis; 41.4% of participants were male, and the average age was 64.79 (± 8.76). In our study, we showed a positive correlation of homocysteine with FRS. In the logistic regression models, higher ln[homocysteine] levels was associated with higher CVD risk with a odds ratio (OR) of 2.499 and 95% confidence interval (CI) of 1.214 to 5.142 in the high homocysteine level group compared with the low homocysteine group after adjusting for traditional CVD risk factors. The area under the ROC curve was 0.667, and a ln[homocysteine] cut-off value of 2.495 µmol/L was determined.

Conclusions

Middle-aged and elderly people with increased homocysteine levels were associated with higher FRSs in this Taiwan community. Furthermore, homocysteine was an independent risk factor for high CVD risk in this study.
Correlation between the geographical origin of Helicobacter pylori homB-positive strains and their clinical outcomes: a systematic review and meta-analysis
Authors: Keikha Masoud , Karbalaei Mohsen
Published: April 2021

Background

In general, all virulence factors of Helicobacter pylori (H. pylori) are involved in its infections. However, recent studies have shown that the homB gene is one of the virulence genes that affects the severity of the clinical results of this bacterium.

Methods

The main purpose of this study was to investigate the relationship between the presence of homB gene in H. pylori and the progression of its infection to peptic ulcer and gastric cancer. In the present study, we conducted a systematic search to collect all articles related to the effect of homB-positive strains on clinical outcomes. Finally, 12 eligible studies according to our criteria were included in this meta-analysis and the effect of homB gene on gastric ulcer and gastric cancer diseases was evaluated by summary odds ratio (OR).

Results

Current results showed that the homB-positive strains significantly increase the risk of peptic ulcer (OR 1.36; 1.07–1.72 with 95% CIs), especially in western countries (OR 1.61; 1.20–2.14 with 95% CIs). Moreover, we observed a positive association between the homB gene and risk of gastric cancer (OR 2.16; 1.37–3.40 with 95% CIs). In addition, based on subgroup analysis, it was found that the presence of this gene in H. pylori strains increases the risk of gastric cancer in the Asian population (OR 3.71; 1.85–7.45 with 95% CIs).

Conclusions

Overall, in the present study we found that homB gene is responsible for the progressing of primary infection to severe complications, in particular peptic ulcer in western countries and gastric cancer in Asian countries.
Predictors of kidney function recovery among incident ESRD patients
Authors: Santos Maria , Yin Huiying , Steffick Diane , Saran Rajiv , Heung Michael
Published: April 2021

Background

ESRD is considered an irreversible loss of renal function, yet some patients will recover kidney function sufficiently to come off dialysis. Potentially modifiable predictors of kidney recovery, such as dialysis prescription, have not been fully examined.

Methods

Retrospective cohort study using United States Renal Data System (USRDS) data to identify incident hemodialysis (HD) patients between 2012 and 2016, the first 4 years for which dialysis treatment data is available. The primary outcome was kidney recovery within 1 year of ESRD and HD initiation, defined by a specific recovery code and survival off dialysis for at least 30 days. Patient and treatment characteristics were compared between those that recovered versus those that remained dialysis-dependent. A time-dependent survival model was used to identify independent predictors of kidney recovery.

Results

During the study period, there were 372,387 incident HD patients with available data, among whom 16,930 (4.5%) recovered to dialysis-independence. Compared to non-recovery, a higher proportion of patients with kidney recovery were of white race, and non-Hispanic ethnicity. Both groups had a similar age distribution. Patients with an acute kidney injury diagnosis as primary cause of ESRD were most likely to recover, but the most common ESRD diagnosis among recovering patients was type 2 diabetes (29.8% of recovery cases). Higher eGFR and lower albumin at ESRD initiation were associated with increased likelihood of recovery. When examining HD ultrafiltration rate (UFR), each quintile above the first quintile was associated with a progressively lower likelihood of recovery (HR 0.45, 95% CI 0.43–0.48 for highest versus lowest quintile, p < 0.001).

Conclusions

We identified non-modifiable and potentially modifiable factors associated with kidney recovery which may assist clinicians in counseling and monitoring incident ESRD patients with a greater chance to gain dialysis-independence. Clinical trials are warranted to examine the impact of dialysis prescription on subsequent kidney function recovery.
Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells
Authors: Wu Youliang , Meng Delong , Xu Xin , Bao Junjun , You Yexiang , Sun Yanjun , Li Yongxiang , Sun Dengqun
Published: April 2021

Background

Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In this study, we investigated the expression, clinical significance and biological function of INPP4B in GBC patients and cell lines.

Methods

The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analysed. Knockdown and overexpression of INPP4B in GBC-SD and SGC-996 cells followed by cell proliferation, clonogenic, apoptosis detection, scratch wound-healing and transwell assays were used to identify INPP4B function in vitro.

Results

INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues and was related to histopathological differentiation (p = 0.026). Here, we observed that INPP4B was highly expressed in high-moderately differentiated tumours compared with low-undifferentiated tumours (p = 0.022). Additionally, we found that INPP4B expression was not associated with overall survival of GBC patients (p = 0.071) and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and the prognosis of GBC based on histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression depending on the degree of differentiation. In addition, INPP4B knockdown inhibited the proliferation, colony formation, migration and invasion in GBC cells, while INPP4B overexpression had the opposite effects in vitro, which indicates its role as an oncoprotein.

Conclusions

These findings suggested that INPP4B may play a dual role in the prognosis of GBC depending on the degree of differentiation and that INPP4B might act as an oncogene in gallbladder cancer cells.
Active behavior of triple-negative breast cancer with adipose tissue invasion: a single center and retrospective review
Authors: Yamaguchi Junzo , Moriuchi Hiroki , Ueda Takashi , Kawashita Yujo , Hazeyama Takanori , Tateishi Masaki , Aoki Shigehisa , Uchihashi Kazuyoshi , Nakamura Mikio
Published: April 2021

Background

Interactions between adipocyte and breast cancer (BC) cells have yet to be fully elucidated. Here we investigated the prognostic impact of marginal adipose tissue invasion in both luminal breast cancer (HR+/HER2-) and triple-negative breast cancer (TNBC) (HR−/HER2-).

Methods

A total of 735 patients with early-stage invasive BC (1999–2014) were retrospectively registered. Median length of patient follow-up was 8.9 years. Survival curves were calculated using a Kaplan-Meier cumulative survival plot. The prognostic difference between two groups were assessed by the univariate Cox-proportional hazard regression model.

Results

Patients with adipose tissue invasion (n = 614) had a significantly poorer prognosis than those without adipose tissue invasion (n = 121) in overall survival (OS) (hazard ratio, 2.1; 95% Confidence interval [CI], 1.1 to 4.0; P = 0.025). While a poorer prognosis was observed in TNBC (n = 137) than in luminal BC patients (n = 496) (hazard ratio, 0.45; 95% CI, 0.30 to 0.68, P < 0.001), this aggressive nature of TNBC was noted in node-positive disease (hazard ratio, 0.3; 95% CI, 0.18 to 0.5, P < 0.001) but not in node-negative disease (hazard ratio, 0.78; 95% CI, 0.39 to 1.55, P = 0.472), and also noted in adipose tissue invasion-positive patients (hazard ratio, 0.4; 95% CI, 0.26 to 0.6, P < 0.001) but not in adipose tissue invasion-negative patients (hazard ratio, 0.73; 95% CI, 0.16 to 3.24, P = 0.675). In addition, although patients suffering from TNBC with adipose tissue invasion had a poorer outcome than those without adipose tissue invasion (hazard ratio, 3.63; 95% CI, 1.11 to 11.84; P = 0.033), the difference was not observed in luminal BC (hazard ratio, 1.75; 95% CI, 0.64 to 4.82; P = 0.277).

Conclusions

Adipose tissue invasion was correlated with poor survival in TNBC. Cancer cell invasion into local fat may be a first step on cancer progression and systemic disease in TNBC.
Efficacy of Mobile phone use on adherence to Nevirapine prophylaxis and retention in care among the HIV-exposed infants in prevention of mother to child transmission of HIV: a randomized controlled trial
Authors: Kebaya Lilian M. N. , Wamalwa Dalton , Kariuki Nyambura , Admani Bashir , Ayieko Philip , Nduati Ruth
Published: April 2021

Background

HIV is a major contributor to infant mortality. A significant gap remains between the uptake of infant and maternal antiretroviral regimens and only a minority of HIV-exposed infants receives prophylaxis and safe infant feeding. Losses to follow-up of HIV-exposed infants are associated with shortcomings of facility-based PMTCT models with weak community support of linkages. Use of mobile phones offers an opportunity for improving care and promoting retention assessed by timely attendance of scheduled appointments for the mother-baby pairs and achievement of an HIV-free generation. The objective of this study was to compare self-reported adherence to infant Nevirapine (NVP) prophylaxis and retention in care assessed by timely attendance of scheduled appointments over 10 weeks in HIV exposed infants randomized to 2-weekly mobile phone calls (intervention) versus no phone calls (control).

Methods

In this open label randomized controlled study, one hundred and fifty HIV infected women drawn from 3 health facilities in Western Kenya and their infants were randomly assigned to receive either phone-based reminders on PMTCT messages or standard health care messages (no calls) within 24 h of delivery. Women in the intervention arm continued to receive fortnightly phone calls. At 6- and 10-weeks following randomization we collected data on infant adherence to Nevirapine, mode of infant feeding, early HIV testing and retention in care in both study arms. All analyses were intention to treat.

Results

At 6 weeks follow-up, 90.7% (n = 68) of participants receiving phone calls reported adherence to infant NVP prophylaxis, compared with 72% (n = 54) of participants in the control group (p = 0.005). Participants in the intervention arm were also significantly more likely to remain in care than participants in the control group [78.7% (n = 59) vs. 58.7% (n = 44), p = 0.009 at 6 weeks and 69.3% (n = 52) vs. 37.3% (n = 28), p < 0.001 at 10 weeks].

Conclusions

These results suggest that phone calls are potentially an important tool to improve adherence to infant NVP prophylaxis and retention in care for HIV-exposed infants.

Trial registration

PACTR202007654729602. Registered 6 June 2018 - Retrospectively registered, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3449
Validated screening tools to identify common mental disorders in perinatal and postpartum women in India: a systematic review and meta-analysis
Authors: Fellmeth Gracia , Harrison Siân , Opondo Charles , Nair Manisha , Kurinczuk Jennifer J. , Alderdice Fiona
Published: April 2021

Background

Perinatal common mental disorders are associated with significant adverse outcomes for women and their families, particularly in low- and middle-income settings. Early detection through screening with locally-validated tools can improve outcomes.

Methods

We searched MEDLINE, Embase, PsycINFO, Global Health, Cochrane Library, Web of Science and Google Scholar for articles on the validation of screening tools for common mental disorders in perinatal women in India, with no language or date restrictions. Quality was assessed using the QUADAS-2 tool. We used bivariate and hierarchical summary receiver operating characteristic models to calculate pooled summary estimates of sensitivity and specificity. Heterogeneity was assessed by visualising the distance of individual studies from the summary curve.

Results

Seven studies involving 1003 women were analysed. All studies assessed the validity of the Edinburgh Postnatal Depression Scale (EPDS) in identifying perinatal depression. No validation studies of any other screening tools were identified. Using a common threshold of ≥13 the EPDS had a pooled sensitivity and specificity of 88·9% (95%CI 77·4–94·9) and 93·4 (95%CI 81·5–97·8), respectively. Using optimal thresholds (range ≥ 9 to ≥13) the EPDS had a pooled sensitivity and specificity of 94·4% (95%CI 81·7–98·4) and 90·8 (95%CI 83·7–95·0), respectively.

Conclusion

The EPDS is psychometrically valid in diverse Indian settings and its use in routine maternity care could improve detection of perinatal depression. Further research is required to validate screening tools for other perinatal common mental disorders in India.
Standardized artificially created stable pertrochanteric femur fractures present more homogenous results compared to osteotomies for orthopaedic implant testing
Authors: Schader J.F. , Zderic I. , Gehweiler D. , Dauwe J. , Mys K. , Danker C. , Acklin Y. P. , Sommer C. , Gueorguiev B. , Stoffel K.
Published: April 2021

Background

With regard to biomechanical testing of orthopaedic implants, there is no consensus on whether artificial creation of standardized bone fractures or their simulation by means of osteotomies result in more realistic outcomes. Therefore, the aim of this study was to artificially create and analyze in an appropriate setting the biomechanical behavior of standardized stable pertrochanteric fractures versus their simulation via osteotomizing.

Methods

Eight pairs of fresh-frozen human cadaveric femora aged 72.7 ± 14.9 years (range 48–89 years) were assigned in paired fashion to two study groups. In Group 1, stable pertrochanteric fractures AO/OTA 31-A1 were artificially created via constant force application on the anterior cortex of the femur through a blunt guillotine blade. The same fracture type was simulated in Group 2 by means of osteotomies. All femora were implanted with a dynamic hip screw and biomechanically tested in 20° adduction under progressively increasing physiologic cyclic axial loading at 2 Hz, starting at 500 N and increasing at a rate of 0.1 N/cycle. Femoral head fragment movements with respect to the shaft were monitored by means of optical motion tracking.

Results

Cycles/failure load at 15° varus deformation, 10 mm leg shortening and 15° femoral head rotation around neck axis were 11324 ± 848/1632.4 ± 584.8 N, 11052 ± 1573/1605.2 ± 657.3 N and 11849 ± 1120/1684.9 ± 612.0 N in Group 1, and 10971 ± 2019/1597.1 ± 701.9 N, 10681 ± 1868/1568.1 ± 686.8 N and 10017 ± 4081/1501.7 ± 908.1 N in Group 2, respectively, with no significant differences between the two groups, p ≥ 0.233.

Conclusion

From a biomechanical perspective, by resulting in more consistent outcomes under dynamic loading, standardized artificial stable pertrochanteric femur fracture creation may be more suitable for orthopaedic implant testing compared to osteotomizing the bone.
The CAST study protocol: a cluster randomized trial assessing the effect of circumferential casting versus plaster splinting on fracture redisplacement in reduced distal radius fractures in adults
Authors:   on behalf of the CAST study group, Barvelink Britt , Reijman Max , Schep Niels W. L. , Brown Vanessa , Kraan Gerald A. , Gosens Taco , Polinder Suzanne , Ista Erwin , Verhaar Jan A. N. , Colaris Joost W.
Published: April 2021

Background

There is no consensus concerning the optimal casting technique for displaced distal radius fractures (DRFs) following closed reduction. This study evaluates whether a splint or a circumferential cast is most optimal to prevent fracture redisplacement in adult patients with a reduced DRF. Additionally, the cost-effectiveness of both cast types will be calculated.

Methods/design

This multicenter cluster randomized controlled trial will compare initial immobilization with a circumferential below-elbow cast versus a below-elbow plaster splint in reduced DRFs. Randomization will take place on hospital-level (cluster, n = 10) with a cross-over point halfway the inclusion of the needed number of patients per hospital. Inclusion criteria comprise adult patients (≥ 18 years) with a primary displaced DRF which is treated conservatively after closed reduction. Multiple trauma patients (Injury Severity Score ≥ 16), concomitant ulnar fractures (except styloid process fractures) and patients with concomitant injury on the ipsilateral arm or inability to complete study forms will be excluded. Primary study outcome is fracture redisplacement of the initial reduced DRF. Secondary outcomes are patient-reported outcomes assessed with the Disability Arm Shoulder Hand score (DASH) and Patient-Rated Wrist Evaluation score (PRWE), comfort of the cast, quality of life assessed with the EQ-5D-5L questionnaire, analgesics use, cost-effectiveness and (serious) adverse events occurence. In total, 560 patients will be included and followed for 1 year. The estimated time required for inclusion will be 18 months.

Discussion

The CAST study will provide evidence whether the type of cast immobilization is of influence on fracture redisplacement in distal radius fractures. Extensive follow-up during one year concerning radiographic, functional and patient reported outcomes will give a broad view on DRF recovery.

Trial registration

Registered in the Dutch Trial Registry on January 14th 2020. Registration number: NL8311.
Salvia miltiorrhiza hydroalcoholic extract inhibits postoperative peritoneal adhesions in rats
Authors: Raisi Abbas , Dezfoulian Omid , Davoodi Farshid , Taheri Shayan , Ghahremani Soroush Afshar
Published: April 2021

Background

One of the most prevalent postoperative complications is believed to be intra-abdominal peritoneal adhesions, which is followed by several complications. Several adhesion prevention products have been examined, yet none of them were found to be completely effective. The current research is conducted to evaluate the beneficial effects of Salvia miltiorrhiza hydroalcoholic extract in inhibiting postoperative peritoneal adhesions in rats.

Methods

Forty rats were randomly classified into five equal groups (n = 8): 1) the normal group did not undergo surgical operations, 2) the control group in which the adhesion was induced, and which did not receive any treatment, 3) distilled water group that received distilled water, and 4,5) treatment groups treated with 1 and 5% of Salvia miltiorrhiza hydroalcoholic extract. The rats were euthanized 14 days following the surgery and the macroscopic score, the microscopic score of granulomatous inflammation and granulation tissue formation, IHC markers (vimentin, CD31, IL-1β, COX-2, and iNOS), and oxidative stress biomarkers (MDA, GPx, CAT, and TAC) were assessed in the experimental groups of the study.

Results

The difference between the control group and other groups for the adhesions macroscopic score, microscopic score, IHC markers, and oxidative stress biomarkers was significant (p < 0.05). Distilled water had no protective effect on the formation of peritoneal adhesions. Salvia miltiorrhiza treatment in two different doses significantly reduced macroscopic and microscopic scores, MDA concentration, Vimentin, IL-1β, COX-2, and iNOS compared to the control group (p < 0.05). The levels of GPx, CAT, and TAC in the treatment groups increased significantly compared with the control group (p < 0.05). Our findings revealed that a higher dose of Salvia miltiorrhiza was more effective in reducing peritoneal adhesions, proinflammatory and mesenchymal cell markers, and oxidative stress.

Conclusions

Salvia miltiorrhiza extract, owing to its strong antioxidant and anti-inflammatory properties, could effectively reduce peritoneal adhesions. Therefore, Salvia miltiorrhiza is recommended to be used as an effective anti-peritoneal post-operative adhesive agent.
The capacity of primary health care facilities in Saudi Arabia: infrastructure, services, drug availability, and human resources
Authors: Al Saffer Quds , Al-Ghaith Taghred , Alshehri Ahlam , Al-Mohammed Rimah , Al Homidi Shahad , Hamza Mariam M. , Herbst Christopher H. , Alazemi Nahar
Published: April 2021

Background

Primary healthcare (PHC) is an essential component of an effective healthcare system. The Kingdom of Saudi Arabia’s (KSA) health reforms prioritize tackling the increasing noncommunicable disease burden by prioritizing PHC, centering it as the core of the newly proposed Model of Care. To identify challenges and opportunities to scale up PHC capacity, understanding the current capacity of primary health care centers (PHCC) is critical. A limited number of publications review PHC capacity in KSA, focusing on specific regions/sectors; this paper is a first to examine PHC capacity on a national level.

Methods

The study uses a countrywide Facility Survey that collected data in 2018 from 2319 PHCCs, generating information on their characteristics, number of health workers, services provided, and capacity elements captured through the Service Availability and Drug Availability constructed indices. Descriptive analysis was performed by rural-urban classification. Ordinary Least Squares (OLS) regressions were used to understand correlates to health workers and equipment availability. Finally, a logistic regression was fitted for selected services. Regressions controlled for various measures to determine correlates with facilities’ capacity.

Results

On a national level, there are 0.74 PHCCs per 10,000 population in KSA. There are variations in the distribution of PHCCs across regions and within regions across rural and urban areas. PHCCs in urban areas have more examination rooms but lower examination room densities. Offering 24 × 7 services in PHCCs is infrequent and dependency on paper-based medical recording remains common. More urban regions are more likely to offer general services but less likely to offer burn management and emergency services. PHCCs are mostly staffed with general medicine, family medicine, and obstetrics & gynecology physicians, whose numbers are more concentrated in urban areas; however, their densities are higher in rural areas. Finally, psychiatrists and nutritionists are rare to find in PHCCs.

Conclusions

Decision-makers need to consider several factors when designing PHC policies. For instance, PHC accreditation needs to be prioritized given its positive correlation with service provision and health workers availability. PHC 24 × 7 operation also needs considerations in rural areas due to the high dependency on PHCCs. Finally, there is a substantial need for improvements in e-health.
Maintaining Plasmodium falciparum gametocyte infectivity during blood collection and transport for mosquito feeding assays in the field
Authors: Soumare Harouna M. , Guelbeogo Wamdaogo Moussa , van de Vegte-Bolmer Marga , van Gemert Geert-Jan , Soumanaba Zongo , Ouedraogo Alphonse , Ouattara Maurice S. , Abdullahi Ahmad , Jadama Lamin , Camara Muhammed M. , Gaye Pa Modou , Mendy Michael , Davis Nwakanma , Tiono Alfred B. , D’Alessandro Umberto , Drakeley Chris , Bousema Teun , Moreno Marta , Collins Katharine A.
Published: April 2021

Background

Mosquito feeding assays using venous blood are commonly used for evaluating the transmission potential of malaria infected individuals. To improve the accuracy of these assays, care must be taken to prevent premature activation or inactivation of gametocytes before they are fed to mosquitoes. This can be challenging in the field where infected individuals and insectary facilities are sometimes very far apart. In this study, a simple, reliable, field applicable method is presented for storage and transport of gametocyte infected blood using a thermos flask.

Methods

The optimal storage conditions for maintaining the transmissibility of gametocytes were determined initially using cultured Plasmodium falciparum gametocytes in standard membrane feeding assays (SMFAs). The impact of both the internal thermos water temperature (35.5 to 37.8 °C), and the external environmental temperature (room temperature to 42 °C) during long-term (4 h) storage, and the impact of short-term (15 min) temperature changes (room temp to 40 °C) during membrane feeding assays was assessed. The optimal conditions were then evaluated in direct membrane feeding assays (DMFAs) in Burkina Faso and The Gambia where blood from naturally-infected gametocyte carriers was offered to mosquitoes immediately and after storage in thermos flasks.

Results

Using cultured gametocytes in SMFAs it was determined that an internal thermos water temperature of 35.5 °C and storage of the thermos flask between RT (~ 21.3 °C) and 32 °C was optimal for maintaining transmissibility of gametocytes for 4 h. Short-term storage of the gametocyte infected blood for 15 min at temperatures up to 40 °C (range: RT, 30 °C, 38 °C and 40 °C) did not negatively affect gametocyte infectivity. Using samples from natural gametocyte carriers (47 from Burkina Faso and 16 from The Gambia), the prevalence of infected mosquitoes and the intensity of oocyst infection was maintained when gametocyte infected blood was stored in a thermos flask in water at 35.5 °C for up to 4 h.

Conclusions

This study determines the optimal long-term (4 h) storage temperature for gametocyte infected blood and the external environment temperature range within which gametocyte infectivity is unaffected. This will improve the accuracy, reproducibility, and utility of DMFAs in the field, and permit reliable comparative assessments of malaria transmission epidemiology in different settings.
Application of the ACOSOG Z0011 criteria to Chinese patients with breast cancer: a prospective study
Authors: Peng Yuan , Liu Miao , Li Xianan , Tong Fuzhong , Cao Yingming , Liu Peng , Zhou Bo , Liu Hongjun , Cheng Lin , Guo Jiajia , Xie Fei , Yang Houpu , Wang Siyuan , Wang Chaobin , Chen Yalin , Wang Shu
Published: April 2021

Background

Although the ACOSOG Z0011 study showed that axillary lymph node dissection (ALND) could be avoided in a specific population of sentinel lymph node-positive patients, it is not widely accepted by Chinese surgeons. We conducted a prospective single-arm study to confirm whether or not the results of Z0011 are applicable to Chinese patients.

Methods

Patients conforming to the Z0011 criteria were prospectively enrolled at the Peking University People’s Hospital Breast Center from November 2014 to June 2019. The clinicopathological features of the study group were compared with those of the Z0011 study group. Lymphedema after surgery, the incidence of local-regional recurrence, and survival were analyzed.

Results

One hundred forty-two patients who met the Z0011 eligibility criteria were enrolled in this study; 115 underwent sentinel lymph node biopsy (SLNB) alone. Compared with the Z0011 trial, younger patients were included (median age, 52 [26–82] years vs 54 [25–90] years; P = 0.03). For clinical T stage, tumor histology, hormone status, lymphovascular invasion, and the number of positive sentinel lymph nodes (SLNs), no statistically significant differences were observed. More patients received adjuvant chemotherapy and endocrine therapy in this study (90.85% vs 58.0% and 80.99% vs 46.6% respectively, P <0.001). A similar percentage of patients received radiotherapy, but more nodal radiotherapy procedures were carried out in our study (54.5% vs 16.9%). After a median follow-up of 29 months, only 1 patient (0.9%) had ipsilateral breast tumor recurrence, and no regional recurrence occurred.

Conclusion

Our study showed that it is achievable to avoid ALND in patients eligible for Z0011 in China.

Trial registration

ClinicalTrials.gov. Registration number NCT03606616. Retrospectively registered on 31 July 2018.
Key proteins of invadopodia are overexpressed in oral squamous cell carcinoma suggesting an important role of MT1-MMP in the tumoral progression
Authors: Mitre Geovanni Pereira , Balbinot Karolyny Martins , Ribeiro André Luis Ribeiro , da Silva Kataoka Maria Sueli , de Melo Alves Júnior Sérgio , de Jesus Viana Pinheiro João
Published: April 2021

Background

Oral squamous cell carcinoma (OSCC) is the most relevant malignant neoplasm among all head and neck tumours due to its high prevalence and unfavourable prognosis. Tumour invasion and metastasis that affect prognosis are result of a set of complex events that cells with invasive potential use to spread to other regions. These cells use several mechanisms to invade tissues, including a type of finger-like membrane protrusion called invadopodia. This study aims to investigate the immunoexpression of invaopodia related-proteins TKs5, cortactin, TKs4 and MT1-MMP in OSCC and correlate it to clinicopathological data.

Methods

An immunohistochemical evaluation of fifty cases of OSCCs and 20 cases of oral mucosa (OM) were assessed. The expression of invadopodia proteins were analysed in comparison to normal tissue (OM) and correlated to different clinical-stage and histological grade of OSCC.

Results

TKs5, cortactin, TKs4 and MT1-MMP were significantly overexpressed in OSCC when compared to OM (p < 0.0001). Among tumour stages, TKs5 showed a statistical difference in immunolabelling between stage I and III (p = 0.026). Cortactin immunolabelling was statistically higher in grade I than in grade II and III. No differences were seen on TKs4 expression based on tumour staging or grading. MT1-MMP was higher expressed and showed statistical difference between stages I and III and grades I compared to II and III.

Conclusions

The invadopodia related-proteins were found to be overexpressed in OSCC when compared to OM, suggesting invadopodia formation and activity. Besides overexpressed in OSCC, cortactin, TKs4 and TKs5 showed no or ambiguous differences in protein expression when compared among clinical-stages or histological grades groups. Conversely, the expression of MT1-MMP increased in advanced stages and less differentiated tumours, suggesting MT1-MMP expression as a promising prognostic marker in OSCC.
Identification of key genes and pathways of BMP-9-induced osteogenic differentiation of mesenchymal stem cells by integrated bioinformatics analysis
Authors: Wu Jia-qi , Mao Lin-bo , Liu Ling-feng , Li Yong-mei , Wu Jian , Yao Jiao , Zhang Feng-huan , Liu Ting-yu , Yuan Ling
Published: April 2021

Background

The purpose of present study was to identify the differentially expressed genes (DEGs) associated with BMP-9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) by using bioinformatics methods.

Methods

Gene expression profiles of BMP-9-induced MSCs were compared between with GFP-induced MSCs and BMP-9-induced MSCs. GSE48882 containing two groups of gene expression profiles, 3 GFP-induced MSC samples and 3 from BMP-9-induced MSCs, was downloaded from the Gene Expression Omnibus (GEO) database. Then, DEGs were clustered based on functions and signaling pathways with significant enrichment analysis. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that the identified DEGs were potentially involved in cytoplasm, nucleus, and extracellular exosome signaling pathway.

Results

A total of 1967 DEGs (1029 upregulated and 938 downregulated) were identified from GSE48882 datasets. R/Bioconductor package limma was used to identify the DEGs. Further analysis revealed that there were 35 common DEGs observed between the samples. GO function and KEGG pathway enrichment analysis, among which endoplasmic reticulum, protein export, RNA transport, and apoptosis was the most significant dysregulated pathway. The result of protein-protein interaction (PPI) network modules demonstrated that the Hspa5, P4hb, Sec61a1, Smarca2, Pdia3, Dnajc3, Hyou1, Smad7, Derl1, and Surf4 were the high-degree hub nodes.

Conclusion

Taken above, using integrated bioinformatical analysis, we have identified DEGs candidate genes and pathways in BMP-9 induced MSCs, which could improve our understanding of the key genes and pathways for BMP-9-induced osteogenic of MSCs.
The ACTyourCHANGE study protocol: promoting a healthy lifestyle in patients with obesity with Acceptance and Commitment Therapy—a randomized controlled trial
Authors: Guerrini Usubini Anna , Cattivelli Roberto , Giusti Emanuele Maria , Riboni Francesco Vailati , Varallo Giorgia , Pietrabissa Giada , Manzoni Gian Mauro , Consoli Simone , Bastoni Ilaria , Granese Valentina , Volpi Clarissa , Villa Valentina , Caretti Annalisa , Bottacchi Michela , Castelnuovo Gianluca , Molinari Enrico
Published: April 2021

Background

As treatment of choice in promoting psychological flexibility, Acceptance and Commitment Therapy (ACT) was found to be effective in several conditions, and among different populations, including weight management in individuals with obesity. However, the mechanism of action of psychological flexibility is less known. The aim of the present study is, within the context of a brief ACT intervention for behavioral change and behavioral maintenance of a healthy lifestyle in a sample of inpatients with obesity, to explore the effect of each subcomponent of the psychological flexibility model on treatment processes and outcomes.

Methods

A randomized controlled trial will be conducted. Ninety Italian adult inpatients with obesity attending a rehabilitation program for weight loss will be randomly allocated into three experimental conditions targeting respectively each subcomponent of the psychological flexibility model: group Engage focused on values-oriented behaviors, group Openness focused on acceptance and cognitive defusion, and group Awareness focused on being present and aware of thoughts, feelings, and behaviors at every moment. Weight, BMI (kg/m2), the Psychological General Well-Being Inventory (PGWBI), the Outcome Questionnaire-45.2 (OQ-45.2), the Depression Anxiety and Stress Scale (DASS-21), the Difficulties in Emotion Regulation Scale (DERS), the Dutch Eating Behaviors Questionnaire (DEBQ), the Brief Values Inventory (BVI), the Committed Action Questionnaire (CAQ), the Italian-Cognitive Fusion Questionnaire (I-CFQ), the Five Facet Mindfulness Questionnaire (FFMQ), and the Acceptance and Action Questionnaire (AAQ-II) will be assessed at the beginning (time 0), at the end of psychological intervention (time 1), and after 3 (time 2) and 6 months (time 3) and 9 months (time 4) from discharge. During the following month after discharge, outpatients will be monitored in their adherence to a healthy lifestyle, using a wearable device.

To assess the effectiveness of the intervention, mixed between-within 3 (conditions) × 4 (times) repeated measure ANOVAs will be conducted to examine changes from time 0 to time 1, 2, 3, and 4 in means of weight, BMI, and means of scores PGWBI, OQ-45.2, DASS, DERS, DEBQ, AAQ-II, BVI, CAQ, I-CFQ, and FFMQ, between three groups.

Discussion

This study will contribute to clarify the mechanism of action of each subcomponent of the psychological flexibility model and understand its impact on the promotion of a healthy lifestyle.

Trial registration

ClinicalTrials.govNCT04474509. Registered on July 4, 2020
Optimized polyepitope neoantigen DNA vaccines elicit neoantigen-specific immune responses in preclinical models and in clinical translation
Authors: Li Lijin , Zhang Xiuli , Wang Xiaoli , Kim Samuel W. , Herndon John M. , Becker-Hapak Michelle K. , Carreno Beatriz M. , Myers Nancy B. , Sturmoski Mark A. , McLellan Michael D. , Miller Christopher A. , Johanns Tanner M. , Tan Benjamin R. , Dunn Gavin P. , Fleming Timothy P. , Hansen Ted H. , Goedegebuure S. Peter , Gillanders William E.
Published: April 2021

Background

Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation.

Methods

We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer models through genome sequencing and in silico neoantigen prediction pipelines. Optimized polyepitope neoantigen DNA vaccines specific for the murine breast tumor E0771 and 4T1 were designed and their immunogenicity was tested in vivo. We also tested an optimized polyepitope neoantigen DNA vaccine in a patient with metastatic pancreatic neuroendocrine tumor.

Results

Our data support an optimized polyepitope neoantigen DNA vaccine design encoding long (≥20-mer) epitopes with a mutant form of ubiquitin (Ubmut) fused to the N-terminus for antigen processing and presentation. Optimized polyepitope neoantigen DNA vaccines were immunogenic and generated robust neoantigen-specific immune responses in mice. The magnitude of immune responses generated by optimized polyepitope neoantigen DNA vaccines was similar to that of synthetic long peptide vaccines specific for the same neoantigens. When combined with immune checkpoint blockade therapy, optimized polyepitope neoantigen DNA vaccines were capable of inducing antitumor immunity in preclinical models. Immune monitoring data suggest that optimized polyepitope neoantigen DNA vaccines are capable of inducing neoantigen-specific T cell responses in a patient with metastatic pancreatic neuroendocrine tumor.

Conclusions

We have developed and optimized a novel polyepitope neoantigen DNA vaccine platform that can target multiple neoantigens and induce antitumor immune responses in preclinical models and neoantigen-specific responses in clinical translation.
Utilizing asynchronous email interviews for health research: overview of benefits and drawbacks
Authors: Amri Michelle , Angelakis Christina , Logan Dilani
Published: April 2021

Objective

Through collating observations from various studies and complementing these findings with one author’s study, a detailed overview of the benefits and drawbacks of asynchronous email interviewing is provided. Through this overview, it is evident there is great potential for asynchronous email interviews in the broad field of health, particularly for studies drawing on expertise from participants in academia or professional settings, those across varied geographical settings (i.e. potential for global public health research), and/or in circumstances when face-to-face interactions are not possible (e.g. COVID-19).

Results

Benefits of asynchronous email interviewing and additional considerations for researchers are discussed around: (i) access transcending geographic location and during restricted face-to-face communications; (ii) feasibility and cost; (iii) sampling and inclusion of diverse participants; (iv) facilitating snowball sampling and increased transparency; (v) data collection with working professionals; (vi) anonymity; (vii) verification of participants; (viii) data quality and enhanced data accuracy; and (ix) overcoming language barriers. Similarly, potential drawbacks of asynchronous email interviews are also discussed with suggested remedies, which centre around: (i) time; (ii) participant verification and confidentiality; (iii) technology and sampling concerns; (iv) data quality and availability; and (v) need for enhanced clarity and precision.
Antibiotic resistance, biofilm formation, and biofilm-associated genes among Stenotrophomonas maltophilia clinical isolates
Authors: Bostanghadiri Narjess , Ardebili Abdollah , Ghalavand Zohreh , Teymouri Samane , Mirzarazi Mahsa , Goudarzi Mehdi , Ghasemi Ehsan , Hashemi Ali
Published: April 2021

Objective

The purpose of the present study was to investigate the antimicrobial susceptibility pattern, biofilm production, and the presence of biofilm genes among the S. maltophilia clinical isolates. A total of 85 clinical isolates of S. maltophilia were collected from patients referred to several hospitals. Susceptibility to antibiotics was investigated by disc diffusion method according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). By the crystal violet staining method, the capability of biofilm formation was examined. The genes associated with biofilm production were investigated by the PCR-sequencing techniques.

Results

All isolates were resistant to doripenem, imipenem, and meropenem. Minocycline, trimethoprim/sulfamethoxazole and levofloxacin exhibited the highest susceptibility of 100%, 97.65%, and 95.29%, respectively. The results of crystal violet staining assay showed that all isolates (100%) form biofilm. Moreover, 24 (28.23%), 32 (37.65%), and 29 (34.12%) of isolates were categorized as weak, moderate, and strong biofilm producers, respectively. Biofilm genes including rpfF, spgM and rmlA had an overall prevalence of 89.41% (76/85), 100% (85/85) and 84.71% (72/85), respectively. Rational prescribing of antibiotics and implementation of infection control protocols are necessary to prevent further infection and development of antimicrobial resistance. Combination strategies based on the appropriate antibiotics along with anti-biofilm agents can also be selected to eliminate biofilm-associated infections.
Advances in epigenetic therapeutics with focus on solid tumors
Authors: Jin Ning , George Tiffany L. , Otterson Gregory A. , Verschraegen Claire , Wen Haitao , Carbone David , Herman James , Bertino Erin M. , He Kai
Published: April 2021

Epigenetic (“above genetics”) modifications can alter the gene expression without altering the DNA sequence. Aberrant epigenetic regulations in cancer include DNA methylation, histone methylation, histone acetylation, non-coding RNA, and mRNA methylation. Epigenetic-targeted agents have demonstrated clinical activities in hematological malignancies and therapeutic potential in solid tumors. In this review, we describe mechanisms of various epigenetic modifications, discuss the Food and Drug Administration-approved epigenetic agents, and focus on the current clinical investigations of novel epigenetic monotherapies and combination therapies in solid tumors.
Prognostic value of amyloid/tau/neurodegeneration (ATN) classification based on diagnostic cerebrospinal fluid samples for Alzheimer’s disease
Authors: Delmotte Koen , Schaeverbeke Jolien , Poesen Koen , Vandenberghe Rik
Published: April 2021

Objective

The primary study objective of this retrospective academic memory clinic-based observational longitudinal study was to investigate the prognostic value of a cerebrospinal fluid (CSF)-based ATN classification for subsequent cognitive decline during the 3 years following lumbar puncture in a clinical, real-life setting. The secondary objective was to investigate the prognostic value of CSF biomarkers as continuous variables.

Methods

Data from 228 patients (median age 67 (47–85) years), who presented at the Neurology Memory Clinic UZ/KU Leuven between September 2011 and December 2016, were included with a follow-up period of up to 36 months. Patients underwent a CSF AD biomarker test for amyloid-beta 1–42 (Aβ42), hyperphosphorylated tau (p181-tau) and total tau (t-tau) in the clinical work-up for diagnostic reasons. Patients were divided into ATN classes based on CSF biomarkers: Aβ42 for amyloid (A), p181-tau for tau (T), and t-tau as a measure for neurodegeneration (N). Based on retrospective data analysis, cognitive performance was evaluated by Mini Mental State Examination (MMSE) scores every 6 months over a period up to 36 months following the lumbar puncture. The statistical analysis was based on linear mixed-effects modeling (LME).

Results

The distribution in the current clinical sample was as follows: A−/T−/N− 32.02%, A+/T−/N− 33.33%, A+/T+/N+ 17.11%, A+/T−/N+ 11.84%, A−/T−/N+ 4.39%, A−/T+/N+ 1.32% (3 cases), with no cases in the A−/T+/N− and A+/T+/N− class. Hence, the latter 3 classes were excluded from further analyses. The change of MMSE relative to A−/T−/N− over a 36-month period was significant in all four ATN classes: A+/T+/N+ = − 4.78 points on the MMSE; A−/T−/N+ = − 4.76; A+/T−/N+ = − 2.83; A+/T−/N− = − 1.96. The earliest significant difference was seen in the A+/T+/N+ class at 12 months after baseline. The effect of ATN class on future cognitive decline was confirmed for a different set of CSF thresholds. All individual baseline CSF biomarkers including the Aβ42/t-tau ratio showed a significant correlation with subsequent cognitive decline, with the highest correlation seen for Aβ42/t-tau.

Conclusion

ATN classification based on CSF biomarkers has a statistically significant and clinically relevant prognostic value for the course of cognitive decline in a 3-year period in a clinical practice setting.