bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of successful outcome of tubularized incised plate for primary distal hypospadias repair
Authors: Abdelhalim Khaled M. , Abdelwahab Hassan A. , Abdelgawad Esam , Kadry Ahmed M. , Sherief Mahmoud H.
Published: December 2021

Background

Several preoperative factors affect the outcome of Tabularized Incised Plate (TIP) repair. Our aim was to collect and analyze all these factors to define what the most important predictive factors are.

Methods

Hundred patients (1–5 years old) with primary distal hypospadias were included. Exclusion criteria included previous penile operations and hormonal treatment or associated congenital anomalies. Anogenital distance (AGD), stretched penile length (SPL), meatal site, glanular shape, chordee and torsion degree, plate width and glans meatus shaft (GMS) score were assessed. TIP repair was done to all patients and followed up for one year. The outcome was correlated with the above parameters.

Results

Mean ± SD of age of patients was 3.5 ± 1.5 years, while weight was 14.1 ± 3.0 kg. Complication rate was 18% including urethrocutaneous fistula (UCF) and meatal stenosis 14%, repair breakdown 1% and urethral stricture 3%. Patients with chordee degree < 30° and distal penile meatal location were associated with increased risk for complications by 11.6 and 8.2 times; 95% CI was (1.46–91.75) and (1.02–66.52), respectively (p < 0.05 for each). Plate width ≥ 9 mm, AGD > 5 cm, GMS score ≤ 7 (p < 0.001 for each), age of patient ≤ 2 years old, and SPL > 3.5 cm (p < 0.01 for each) were associated with successful outcome of repair.

Conclusion

The proposed successful criteria of TIP repair were absent chordee, coronal/subcoronal penile meatal location, plate width ≥ 9 mm, AGD > 5 cm, age of patient ≤ 2 years old, GMS score ≤ 7, SPL > 3.5 cm and grooved glanular shape.
Sarcopenia and coronary heart disease synergistically increase the risk of new onset depressive symptoms in older adults
Authors: Chen Xiaoyu , Han Peipei , Yu Xing , Zhang Yuanyuan , Song Peiyu , Liu Yuewen , Liu Jinghuan , Tang Jiawei , Zhang Yisong , Zhao Yong , Zheng Jiejiao , Chu Lixi , Wang Hong Bing , Guo Qi
Published: December 2021

Background

Coronary heart disease (CHD), sarcopenia and depression are common disorders that markedly impair quality of life and impose a huge financial burden on society. They are also frequently comorbid, exacerbating condition and worsening prognosis. This study aimed to investigate the additive effects of CHD and sarcopenia on the risk of new onset depressive symptoms in older adults.

Methods

The prospective cohort study comprised 897 Chinese community-dwelling participants who were aged 60 years and older (386 men; mean age 66.9 ± 5.9 years) without depressive symptoms at baseline, recruited from Chadian of Tianjin, China. Sarcopenia was defined according to the Asian Working Group for Sarcopenia (AWGS) criteria. CHD was identified via medical records or new diagnosed by at least two physicians. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS) ≥11. Longitudinal data on new onset depressive symptoms were collected up to 12 months after baseline.

Results

We found that 103 (11.5%) of the 897 participants without depressive symptoms at baseline had developed depressive symptoms. Participants were classified into mutually exclusive groups based on sarcopenia status and CHD: normal, CHD alone, sarcopenia alone, and co-occurring groups. A logistic regression showed that the CHD alone [odd ratios (OR) = 1.78, 95% confidence interval (CI) = 1.05–3.02], sarcopenia alone (OR = 2.79, 95% CI = 1.26–6.22), and co-occurring (OR = 7.19, 95% CI = 2.75–18.81) had higher risk of depressive symptoms than the normal group after adjusting for the covariates.

Conclusions

CHD and sarcopenia synergistically increase the risk of new onset depressive symptoms in older adults. Thus, older adults may require early detection, and appropriate interventions should be implemented.
Gestational week-specific of uterine artery Doppler indices in predicting preeclampsia: a hospital-based retrospective cohort study
Authors: Wu Jiang-Nan , Li Ming-Qing , Xie Feng , Zhang Bin
Published: December 2021

Background

Plenty of studies explored the relationship between uterine artery (UtA) Doppler indices and the onset of preeclampsia at different trimesters. However, few studies test the gestational week-specific predictive value of the UtA indices for subsequent preeclampsia and compare the difference of right or left UtA indices (e.g., pulsatility or resistance index [PI or RI]).

Methods

Hospital-based retrospective cohort study of singleton pregnant women who received the Doppler test between 2012 and 2016 was conducted in 2018. The predictive performance of the UtA indices for preeclampsia and its variants, including early-onset preeclampsia (< 34 weeks) and preterm preeclampsia (< 37 weeks), was estimated.

Results

The UtA indices, with a cutoff value of 1.11 for the right and left UtA-PI, and 0.66 and 0.63 for the right and left UtA-RI, respectively, were effective predictors for subsequent preeclampsia. The prediction was satisfactory at the 9th week of the Doppler scan: areas under the curve ≥ 0.80, the Youden index ranging from 0.54 to 0.58, the sensitivity of 63.2 ~ 73.7%, and the specificity 84.2 ~ 91.3%, respectively. The UtA indices had comparable performance in screening for early-onset and preterm preeclampsia but showed lower predictive value for late-onset cases. Among these indices, the right UtA-RI had the highest specificity (all P < 0.01), while the left UtA-PI showed good authenticity (higher Youden index) in predicting the disorder.

Conclusions

The second-trimester measured UtA indices had a satisfactory performance at the 9th week in predicting subsequent preeclampsia. The right UtA-RI was the first choice in ruling out preeclampsia, while the left UtA-PI showed the best authenticity of the prediction.
A 3D printing personalized percutaneous puncture guide access plate for percutaneous nephrolithotomy: a pilot study
Authors: Keyu Gao , Shuaishuai Li , Raj Ashok , Shuofeng Li , Shuai Liu , Yuan Zhang , Haitao Zhu , Junqi Wang
Published: December 2021

Objective

CT-Urography combined with 3D printing technology, digital design, construction of individualized PCNL puncture guides, and preliminary analyze their efficacy, safety puncture positioning for PCNL.

Methods

Twenty-two patients with renal calculi were randomly selected at the affiliated Hospital of Xuzhou Medical University during 2017–2018. We randomly divided the patients into two groups: in 10 experimental groups, we used our 3D printing personalized percutaneous puncture guide access plate for PCNL, and in the control group, 12 patients with standard USG guide PCNL. The accuracy of puncture position, puncture time, and intraoperative blood loss was compared.

Results

In the experimental group, 10 patients with 3D printing personalized percutaneous puncture guide access plate. The puncture needle was accessed through the guide plate and verified by the color Doppler. The single puncture, needle position, and depth success rate were 100.00% (10/10). The angles were consistent with the preoperative design. In the control group, 12 patients via USG guided PCNL success rate was 75.00% (9/12). The puncture time and amount of hemorrhage was (7.78 ± 0.94) min and (49.31 ± 6.43) mL, and (9.04 ± 1.09) min and (60.08 ± 12.18) mL, respectively. The above data of the two groups were statistically significant (P < 0.05).

Conclusion

3D printing personalized percutaneous nephrolithotomy guide plate for PCNL can improve PCNL renal puncture channel positioning accuracy, shorten puncture time, reduce intraoperative blood loss, bleeding-related complications and provide a new method for PCNL renal puncture positioning, which is worthy of further clinical exploration.
Associations of hypoglycemia, glycemic variability and risk of cardiac arrhythmias in insulin-treated patients with type 2 diabetes: a prospective, observational study
Authors: Andersen Andreas , Bagger Jonatan I. , Sørensen Samuel K. , Baldassarre Maria P. A. , Pedersen-Bjergaard Ulrik , Forman Julie L. , Gislason Gunnar , Lindhardt Tommi B. , Knop Filip K. , Vilsbøll Tina
Published: December 2021

Background

Insulin-treated patients with type 2 diabetes (T2D) are at risk of hypoglycemia, which is associated with an increased risk of cardiovascular disease and mortality. Using a long-term monitoring approach, we investigated the association between episodes of hypoglycemia, glycemic variability and cardiac arrhythmias in a real-life setting.

Methods

Insulin-treated patients with T2D (N = 21, [mean ± SD] age 66.8 ± 9.6 years, BMI 30.1 ± 4.5 kg/m2, HbA1c 6.8 ± 0.4% [51.0 ± 4.8 mmol/mol]) were included for a one-year observational study. Patients were monitored with continuous glucose monitoring ([mean ± SD] 118 ± 6 days) and an implantable cardiac monitor (ICM) during the study period.

Results

Time spend in hypoglycemia was higher during nighttime than during daytime ([median and interquartile range] 0.7% [0.7–2.7] vs. 0.4% [0.2–0.8]). The ICMs detected 724 episodes of potentially clinically significant arrhythmias in 12 (57%) participants, with atrial fibrillation and pauses accounting for 99% of the episodes. No association between hypoglycemia and cardiac arrhythmia was found during daytime. During nighttime, subject-specific hourly incidence of cardiac arrhythmias tended to increase with the occurrence of hypoglycemia (incident rate ratio [IRR] 1.70 [95% CI 0.36–8.01]) but only slightly with increasing time in hypoglycemia (IRR 1.04 [95% CI 0.89–1.22] per 5 min). Subject-specific incidence of cardiac arrhythmias during nighttime increased with increasing glycemic variability as estimated by coefficient of variation whereas it decreased during daytime (IRR 1.33 [95% CI 1.05–1.67] and IRR 0.77 [95% CI 0.59–0.99] per 5% absolute increase, respectively).

Conclusions

Cardiac arrhythmias were common in insulin-treated patients with T2D and were associated with glycemic variability, whereas arrhythmias were not strongly associated with hypoglycemia.

Trial registration: NCT03150030, ClinicalTrials.gov, registered May 11, 2017. https://clinicaltrials.gov/ct2/show/NCT03150030
Metabolic engineering of Corynebacterium glutamicum for producing branched chain amino acids
Authors: Yu Shengzhu , Zheng Bo , Chen Zhenya , Huo Yi-Xin
Published: December 2021

Background

Branched chain amino acids (BCAAs) are widely applied in the food, pharmaceutical, and animal feed industries. Traditional chemical synthetic and enzymatic BCAAs production in vitro has been hampered by expensive raw materials, harsh reaction conditions, and environmental pollution. Microbial metabolic engineering has attracted considerable attention as an alternative method for BCAAs biosynthesis because it is environmentally friendly and delivers high yield.

Main text

Corynebacterium glutamicum(C. glutamicum) possesses clear genetic background and mature gene manipulation toolbox, and has been utilized as industrial host for producing BCAAs. Acetohydroxy acid synthase (AHAS) is a crucial enzyme in the BCAAs biosynthetic pathway ofC. glutamicum, but feedback inhibition is a disadvantage. We therefore reviewed AHAS modifications that relieve feedback inhibition and then investigated the importance of AHAS modifications in regulating production ratios of three BCAAs. We have comprehensively summarized and discussed metabolic engineering strategies to promote BCAAs synthesis inC. glutamicumand offer solutions to the barriers associated with BCAAs biosynthesis. We also considered the future applications of strains that could produce abundant amounts of BCAAs.

Conclusions

Branched chain amino acids have been synthesized by engineering the metabolism ofC. glutamicum. Future investigations should focus on the feedback inhibition and/or transcription attenuation mechanisms of crucial enzymes. Enzymes with substrate specificity should be developed and applied to the production of individual BCAAs. The strategies used to construct strains producing BCAAs provide guidance for the biosynthesis of other high value-added compounds.
p53 signaling in cancer progression and therapy
Authors: Marei Hany E. , Althani Asmaa , Afifi Nahla , Hasan Anwarul , Caceci Thomas , Pozzoli Giacomo , Morrione Andrea , Giordano Antonio , Cenciarelli Carlo
Published: December 2021

The p53 protein is a transcription factor known as the "guardian of the genome" because of its critical function in preserving genomic integrity. The TP53 gene is mutated in approximately half of all human malignancies, including those of the breast, colon, lung, liver, prostate, bladder, and skin. When DNA damage occurs, the TP53 gene on human chromosome 17 stops the cell cycle. If p53 protein is mutated, the cell cycle is unrestricted and the damaged DNA is replicated, resulting in uncontrolled cell proliferation and cancer tumours. Tumor-associated p53 mutations are usually associated with phenotypes distinct from those caused by the loss of the tumor-suppressing function exerted by wild-type p53protein. Many of these mutant p53 proteins have oncogenic characteristics, and therefore modulate the ability of cancer cells to proliferate, escape apoptosis, invade and metastasize. Because p53 deficiency is so common in human cancer, this protein is an excellent option for cancer treatment. In this review, we will discuss some of the molecular pathways by which mutant p53 proteins might perform their oncogenic activities, as well as prospective treatment methods based on restoring tumor suppressive p53 functions.
Risk factors associated with malaria infection identified through reactive case detection in Zanzibar, 2012–2019
Authors: Mkali Humphrey R. , Reaves Erik J. , Lalji Shabbir M. , Al-mafazy Abdul-Wahid , Joseph Joseph J. , Ali Abdullah S. , Abbas Faiza B. , Ali Mohamed H. , Hassan Wahida S. , Kitojo Chonge , Serbantez Naomi , Kabula Bilali I. , Nyinondi Ssanyu S. , Bisanzio Donal , McKay Mike , Eckert Erin , Reithinger Richard , Ngondi Jeremiah M.
Published: December 2021

Background

Over the past two decades, Zanzibar substantially reduced malaria burden. As malaria decreases, sustainable improvements in control interventions may increasingly depend on accurate knowledge of malaria risk factors to further target interventions. This study aimed to investigate the risk factors associated with malaria infection in Zanzibar.

Methods

Surveillance data from Zanzibar’s Malaria Case Notification system from August 2012 and December 2019 were analyzed. This system collects data on malaria cases passively detected and reported by all health facilities (index cases), and household-based reactive case detection (RCD) activities linked to those primary cases. All members of households of the index cases were screened for malaria using a malaria rapid diagnostic test (RDT). Individuals with a positive RDT were treated with artemisinin-based combination therapy. Univariate and multivariate logistic regression analyses were done to investigate the association between RDT positivity among the household members and explanatory factors with adjustment for seasonality and clustering at Shehia level.

Results

A total of 30,647 cases were reported of whom household RCD was completed for 21,443 (63%) index case households and 85,318 household members tested for malaria. The findings show that younger age (p-value for trend [Ptrend] < 0.001), history of fever in the last 2 weeks (odds ratio [OR] = 35.7; 95% CI 32.3–39.5), travel outside Zanzibar in the last 30 days (OR = 2.5; 95% CI 2.3–2.8) and living in Unguja (OR = 1.2; 95% CI 1.0–1.5) were independently associated with increased odds of RDT positivity. In contrast, male gender (OR=0.8; 95% CI 0.7–0.9), sleeping under an LLIN the previous night (OR = 0.9; 95% CI 0.7–0.9), having higher household net access (Ptrend < 0.001), and living in a household that received IRS in the last 12 months (OR = 0.8; 95% CI 0.7–0.9) were independently associated with reduced odds of RDT positivity. A significant effect modification of combining IRS and LLIN was also noted (OR = 0.7; 95% CI 0.6–0.8).

Conclusions

The findings suggest that vector control remains an important malaria prevention intervention: they underscore the need to maintain universal access to LLINs, the persistent promotion of LLIN use, and application of IRS. Additionally, enhanced behavioural change and preventive strategies targeting children aged 5–14 years and travellers are needed.
Health equity impact of community-initiated kangaroo mother care: a randomized controlled trial
Authors: Choudhary Tarun Shankar , Mazumder Sarmila , Haaland Øystein Ariansen , Taneja Sunita , Bahl Rajiv , Martines Jose , Bhan Maharaj Kishan , Johansson Kjell Arne , Sommerfelt Halvor , Bhandari Nita , Norheim Ole F
Published: December 2021

Background

Kangaroo mother care (KMC) can substantially enhance overall survival of low birthweight babies. In a large randomized controlled trial, we recently showed that supporting mothers to provide community initiated KMC (ciKMC) can reduce mortality among infants up to 180 days of life by 25% (hazard ratio (HR) 0.75). With the current analysis, we aimed to explore if ciKMC promotion leads to increased inequity in survival.

Methods

In the trial we randomized 8402 low birthweight babies to a ciKMC (4480 babies) and a control (3922 babies) arm, between 2015 and 2018 in Haryana, India. We estimated the difference in concentration indices, which measure inequality, between babies in the ciKMC and control arms for survival until 180 days of life. Further, we compared the effect of ciKMC promotion across subgroups defined by socioeconomic status, caste, maternal literacy, infant’s sex, and religion.

Results

Our intervention did not increase survival inequity, as the concentration index in the ciKMC arm of the trial was 0.05 (95% CI -0.07 to 0.17) lower than in the control arm. Survival impact was higher among those belonging to the lower two wealth quintiles, those born to illiterate mothers and those belonging to religions other than Hindu.

Conclusions

We found that ciKMC promotion did not increase inequity in survival associated with wealth. The beneficial impact of ciKMC tended to be larger among vulnerable groups. Supporting mothers to provide KMC at home to low birthweight babies will not increase and could indeed reduce inequities in infant survival.

Trial registration

ClinicalTrials.gov, NCT02653534. Registered January 12, 2016—Retrospectively registered.
Surface plasmon resonance biosensor for exosome detection based on reformative tyramine signal amplification activated by molecular aptamer beacon
Authors: Chen Wenqin , Li Zhiyang , Cheng Wenqian , Wu Tao , Li Jia , Li Xinyu , Liu Lin , Bai Huijie , Ding Shijia , Li Xinmin , Yu Xiaolin
Published: December 2021

Human epidermal growth factor receptor 2 (HER2)-positive exosomes play an extremely important role in the diagnosis and treatment options of breast cancers. Herein, based on the reformative tyramine signal amplification (TSA) enabled by molecular aptamer beacon (MAB) conversion, a label-free surface plasmon resonance (SPR) biosensor was proposed for highly sensitive and specific detection of HER2-positive exosomes. The exosomes were captured by the HER2 aptamer region of MAB immobilized on the chip surface, which enabled the exposure of the G-quadruplex DNA (G4 DNA) that could form peroxidase-like G4-hemin. In turn, the formed G4-hemin catalyzed the deposition of plentiful tyramine-coated gold nanoparticles (AuNPs-Ty) on the exosome membrane with the help of H2O2, generating a significantly enhanced SPR signal. In the reformative TSA system, the horseradish peroxidase (HRP) as a major component was replaced with nonenzymic G4-hemin, bypassing the defects of natural enzymes. Moreover, the dual-recognition of the surface proteins and lipid membrane of the desired exosomes endowed the sensing strategy with high specificity without the interruption of free proteins. As a result, this developed SPR biosensor exhibited a wide linear range from 1.0 × 104 to 1.0 × 107 particles/mL. Importantly, this strategy was able to accurately distinguish HER2-positive breast cancer patients from healthy individuals, exhibiting great potential clinical application.

Graphical Abstract
Predictors of poor health-related quality of life among hemodialysis patients with anemia in Jordan
Authors: Alshogran Osama Y. , Shatnawi Esraa A. , Altawalbeh Shoroq M. , Jarab Anan S. , Farah Randa I.
Published: December 2021

Objective

This study examined health-related quality of life (HRQoL) and factors associated with poor HRQoL among hemodialysis (HD) patients.

Methods

A multicenter cross-sectional study was conducted on HD patients with anemia in Jordan (n = 168). Validated questionnaires were utilized to collect data on HRQoL using EQ-5D-5L, psychiatric symptoms using Hospital Anxiety and Depression Scale (HADS), and comorbidities score using the modified Charlson Comorbidity Index (mCCI). Multiple linear regression analysis was conducted to identify the variables which are independently associated with HRQoL among patients.

Results

The mean (± SD) age of study participants was 52.2 (± 14.6) years. The mean utility value of EQ-5D-5L was 0.44 (± 0.42). Participants reported extreme problems mostly in pain/discomfort domain (19.6%). Increased age, increased mCCI and patient complains, more years under dialysis, decreased exercise, and low family income were significantly associated with poor HRQoL (p < 0.05).

Conclusion

The study findings revealed poor HRQoL among HD patients with anemia. Various dimensions of health were negatively affected among HD patients. Development and implementation of appropriate approaches with adequate education and psychosocial support to HD patients by healthcare professionals targeting improved HRQoL and clinical outcomes would be necessary.
The impact of treatment delay on skin cancer in COVID-19 era: a case-control study
Authors: Seretis Konstantinos , Boptsi Eleni , Boptsi Anastasia , Lykoudis Efstathios G.
Published: December 2021

Background

The outbreak of COVID-19 pandemic led to a 2-month lockdown in Europe. Elective surgeries, including skin cancer excisions, were postponed. The purpose of this prospective case-control study was to assess the impact of the treatment delay on patients with non-melanoma skin cancer (NMSC) or melanoma operated in the first post-lockdown period.

Methods

A comparative study of skin cancer operations performed in a 4-month period either in 2020 or in 2019 was conducted. All data were collected from a prospectively maintained clinic database and the pathological reports. Continuous variables were compared with t test or Mann-Whitney U test according to their distribution. Categorical variables were compared with Fisher exact test. Odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the risk of excising high-risk NMSC in 2020 compared with 2019.

Results

Skin cancer excision was performed in 158 cases in 2020 compared to 125 cases in 2019 (26.4% increase). Significantly, more SCC were excised in 2020 (p = 0.024). No significant difference for several clinical parameters regarding BCC, SCC, and melanoma was identified. However, the reconstructive method applied, following NMSC excision, was significantly different, requiring frequently either skin grafting or a flap.

Conclusion

These results indicate that skin cancer treatment delay, due to COVID-19 pandemic, is related to an increased incidence of SCC and more complicated methods of reconstruction. Considering the relapsing COVID-19 waves, significant skin cancer treatment delays should be avoided.

Trial registration

The study adhered to the STROBE statement for case-control studies.
Challenges and opportunities for Iranian global health diplomacy: lessons learned from action for prevention and control of noncommunicable diseases
Authors: Asadi-Lari Mohsen , Ahmadi Teymourlouy Ahmad , Maleki Mohammadreza , Eslambolchi Leila , Afshari Mahnaz
Published: December 2021

Background

The steady rise in noncommunicable diseases (NCDs) worldwide has been a key global health challenge. Governments have the primary responsibility for taking action to prevent and control NCDs. Given the growing importance of globalization of healthcare as well as the increasing use of soft power, governments need to identify challenges and opportunities to enhance global health diplomacy (GHD) for NCD prevention and control. The purpose of this qualitative research was to explain the challenges and opportunities of GHD for NCDs in Iran.

Methods

This study was conducted in 2020 using a qualitative approach and through in-depth, semi-structured interviews with 21 experts and specialists in related fields such as health policy, healthcare management, epidemiology and other related specialties. The participants were selected from all levels of diplomacy, including global, regional and national levels, with at least 3 years of experience in managerial, executive and scientific activities. Data analysis was performed by content analysis with an inductive approach. Data were analysed using inductive content analysis.

Results

The identified challenges were categorized into five main themes, including content challenges, structural challenges, process challenges, governance challenges and cultural challenges. Opportunities extracted from the interviews were also categorized into four main themes, including strong political will, utilizing the capacity of nongovernmental organizations (NGOs), multisectoral collaborations and a well-developed health system.

Conclusions

NCD prevention and control requires a multilateral collaboration-based solution. Recognition of the challenges and opportunities in GHD can help draw significant lessons for building the necessary capacities and implementing more effective policies to prevent and control NCDs.
A novel staging system and clinical predictive nomogram for more accurate staging and prognosis of malignant pancreatic intraductal papillary mucinous neoplasms: a population-based study
Authors: Zhang Haoxiang , Gao Chenggang , Chen Jiaoshun , Wu Shihong , Bai Jianwei , Yin Tao
Published: December 2021

Background

The current guidelines of the American Joint Committee on Cancer (AJCC) for the staging of exocrine pancreatic tumors seem inapplicable to malignant pancreatic intraductal papillary mucinous neoplasms (IPMN). Therefore, we aimed to improve the accuracy of clinical staging and prognosis for malignant IPMN by modifiing current AJCC system.

Methods

We extracted data of 2001 patients with malignant IPMN from the Surveillance, Epidemiology, and End Results database between 2000 and 2016. Of these, 1401 patients were assigned to the primary cohort and 600 patients to the validation cohort.

Results

In Kaplan–Meier analysis of the primary cohort, the current AJCC guidelines were unable to distinguish between certain tumor substages (IA and IB in the 7th, IB and IIA in the 8th). The modified system that we regrouped based on the median overall survival and hazard ratios, was superior in tumor stage classifications. Age > 70 years, tumors located in the body or tail, high-grade differentiated tumors, surgery, chemotherapy, and tumor, lymph node, and metastasis (TNM) stage were identified as independent predictive factors for overall survival. Compared to that of TNM-based systems, the concordance index of the clinical predictive nomogram significantly improved (0.819; 95% confidence interval, 0.805–0.833), with excellent area under the receiver operating characteristic curves (1-, 3-, and 5-year: 0.881, 0.889, and 0.879, respectively). The calibration curves also showed good agreement between prediction and actual observation. The analysis of treatment modalities revealed that surgery resulted in better survival for all resectable malignant IPMN. The analysis of chemotherapy data reveals its potential in improving the prognosis of treatment for patients with locally advanced or distant metastases.

Conclusions

Our modified staging system improves the distinction of tumor stages. The nomogram was a more accurate and clinically reliable tool for prognosis prediction of patients with malignant IPMN.
Long-term memory T cells as preventive anticancer immunity elicited by TuA-derived heteroclitic peptides
Authors: Mauriello Angela , Cavalluzzo Beatrice , Manolio Carmen , Ragone Concetta , Luciano Antonio , Barbieri Antonio , Tornesello Maria Lina , Buonaguro Franco M. , Tagliamonte Maria , Buonaguro Luigi
Published: December 2021

The host’s immune system may be primed against antigens during the lifetime (e.g. microorganisms antigens—MoAs), and swiftly recalled upon growth of a tumor expressing antigens similar in sequence and structure. C57BL/6 mice were immunized in a preventive setting with tumor antigens (TuAs) or corresponding heteroclitic peptides specific for TC-1 and B16 cell lines. Immediately or 2-months after the end of the vaccination protocol, animals were implanted with cell lines. The specific anti-vaccine immune response as well as tumor growth were regularly evaluated for 2 months post-implantation. The preventive vaccination with TuA or their heteroclitic peptides (hPep) was able to delay (B16) or completely suppress (TC-1) tumor growth when cancer cells were implanted immediately after the end of the vaccination. More importantly, TC-1 tumor growth was significantly delayed, and suppressed in 6/8 animals, also when cells were implanted 2-months after the end of the vaccination. The vaccine-specific T cell response provided a strong immune correlate to the pattern of tumor growth. A preventive immunization with heteroclitic peptides resembling a TuA is able to strongly delay or even suppress tumor growth in a mouse model. More importantly, the same effect is observed also when tumor cells are implanted 2 months after the end of vaccination, which corresponds to 8 – 10 years in human life. The observed potent tumor control indicates that a memory T cell immunity elicited during the lifetime by a antigens similar to a TuA, i.e. viral antigens, may ultimately represent a great advantage for cancer patients and may lead to a novel preventive anti-cancer vaccine strategy.
Analysis and validation of m6A regulatory network: a novel circBACH2/has-miR-944/HNRNPC axis in breast cancer progression
Authors: Lv Wenchang , Tan Yufang , Xiong Mingchen , Zhao Chongru , Wang Yichen , Wu Min , Wu Yiping , Zhang Qi
Published: December 2021

Background

N6-methyladenosine (m6A), the most abundant and reversible modification of mRNAs in eukaryotes, plays pivotal role in breast cancer (BC) tumorigenesis and progression. Circular RNAs (circRNAs) can act as tumor promoters or suppressors by microRNA (miRNA) sponges in BC. However, the underlying mechanism of circRNAs in BC progression via regulating m6A modulators remains unclear.

Methods

Prognostic m6A RNA methylation regulators were identified in 1065 BC patients from The Cancer Genome Atlas (TCGA) project. Differentially expressed (DE) miRNAs and DE circRNAs were identified between BC and normal samples in TCGA and GSE101123, respectively. MiRNA-mRNA interactive pairs and circRNA-miRNA interactive pairs were verified by MiRDIP and Circular RNA Interactome. GSEA, KEGG, and ssGSEA were executed to explore the potential biological and immune functions between HNRNPC-high and HNRNPC-low expression groups. qRT-PCR and Western blot were used to quantify the expression of HNRNPC and circBACH2 in MCF-7 and MDA-MB-231 cells. The proliferation of BC cells was assessed by CCK-8 and EdU assay.

Results

2 m6A RNA methylation regulators with prognostic value, including HNRNPC and YTHDF3, were identified in BC patients. Then, the regulatory network of circRNA-miRNA-m6A modulators was constructed, which consisted of 2 DE m6A modulators (HNRNPC and YTHDF3), 12 DE miRNAs, and 11 DE circRNAs. Notably, BC patients with high expression of HNRNPC and low expression of hsa-miR-944 were correlated with late clinical stages and shorter survival times. Besides, the results from the KEGG inferred that the DE HNRNPC was associated with the MAPK signaling pathway in BC. Moreover, the circBACH2 (hsa_circ_0001625) was confirmed to act as hsa-miR-944 sponge to stimulate HNRNPC expression to promote BC cell proliferation via MAPK signaling pathway, thus constructing a circBACH2/hsa-miR-944/HNRNPC axis in BC.

Conclusions

Our findings decipher a novel circRNA-based m6A regulatory mechanism involved in BC progression, thus providing attractive diagnostic and therapeutic strategies for combating BC.
“Forever young at the table”: metabolic effects of eating speed in obesity
Authors: Barrea Luigi , Vetrani Claudia , Verde Ludovica , Napolitano Bruno , Savastano Silvia , Colao Annamaria , Muscogiuri Giovanna
Published: December 2021

Background

Cardiometabolic diseases (CMD) are recognized as the main causes of morbidity and mortality in developed countries. In recent years eating speed (ES) has been of particular interest since some studies have associated it with the development of obesity and CMD. However, the different impact of the ES at which main meals are eaten on the risk of developing these diseases has not yet been identified. Thus, we aimed to investigate the effect of ES at the main meals (breakfast, lunch, and dinner) on the risk of developing cardiometabolic diseases (type 2 diabetes mellitus, dyslipidaemia and hypertension) in middle-aged Caucasian subjects with obesity.

Methods

For this purpose we carried out a cross-sectional, observational study. One hundred and eighty-seven middle-aged subjects aged 43.6 ± 16 years were enrolled of which anthropometric parameters and lifestyle habits were studied. A dietary interview was performed to collect information about meal duration and eating habits at the main meals. According to median value of meal duration, meals were classified in two groups: fast eating group (FEG) and slow eating group (SEG).

Results

The prevalence of dyslipidaemia was more than twice in FEG compared to SEG at lunch and dinner. For all main meals, FEG had a significantly higher risk of dyslipidaemia than SEG (p < 0.05) in unadjusted model. However, when the model was adjusted for age, BMI, physical activity, smoking and alcohol use and medication, the result remained significant for lunch and dinner (p < 0.05).

Conclusion

The results of our study suggest that fast eating increases at lunch and dinner increase the risk of developing dyslipidaemia in obesity.
Prognostic significance of natural killer cell-associated markers in gastric cancer: quantitative analysis using multiplex immunohistochemistry
Authors: Na Hee Young , Park Yujun , Nam Soo Kyung , Koh Jiwon , Kwak Yoonjin , Ahn Sang-Hoon , Park Do Joong , Kim Hyung-Ho , Lee Kyu Sang , Lee Hye Seung
Published: December 2021

Background

Natural killer (NK) cells mediate the anti-tumoral immune response as an important component of innate immunity. The aim of this study was to investigate the prognostic significance and functional implication of NK cell-associated surface receptors in gastric cancer (GC) by using multiplex immunohistochemistry (mIHC).

Methods

We performed an mIHC on tissue microarray slides, including 55 GC tissue samples. A total of 11 antibodies including CD57, NKG2A, CD16, HLA-E, CD3, CD20, CD45, CD68, CK, SMA, and ki-67 were used. CD45 + CD3-CD57 + cells were considered as CD57 + NK cells.

Results

Among CD45 + immune cells, the proportion of CD57 + NK cell was the lowest (3.8%), whereas that of CD57 + and CD57- T cells (65.5%) was the highest, followed by macrophages (25.4%), and B cells (5.3%). CD57 + NK cells constituted 20% of CD45 + CD57 + immune cells while the remaining 80% were CD57 + T cells. The expression of HLA-E in tumor cells correlated with that in tumoral T cells, B cells, and macrophages, but not CD57 + NK cells. The higher density of tumoral CD57 + NK cells and tumoral CD57 + NKG2A + NK cells was associated with inferior survival.

Conclusions

Although the number of CD57 + NK cells was lower than that of other immune cells, CD57 + NK cells and CD57 + NKG2A + NK cells were significantly associated with poor outcomes, suggesting that NK cell subsets play a critical role in GC progression. NK cells and their inhibitory receptor, NKG2A, may be potential targets in GC.
Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma
Authors: Hu Xin , Zhao Guo-Li , Xu Meng-Xi , Zhou Han , Li Fang , Miao Yanying , Lei Bo , Yang Xiong-Li , Wang Zhongfeng
Published: December 2021

Background

Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown.

Methods

A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca2+ image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina.

Results

We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner.

Conclusions

These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.
Maximizing community participation and engagement: lessons learned over 2 decades of field trials in rural Ghana
Authors: Newton Sam , Asbroek Guus Ten , Hill Zelee , Agyemang Charlotte Tawiah , Soremekun Seyi , Etego Seeba Amenga , Kirkwood Betty
Published: December 2021

Background

Successful implementation of community-based research is dominantly influenced by participation and engagement from the local community without which community members will not want to participate in research and important knowledge and potential health benefits will be missed. Therefore, maximising community participation and engagement is key for the effective conduct of community-based research. In this paper, we present lessons learnt over two decades of conducting research in 7 rural districts in the Brong Ahafo region of Ghana with an estimated population of around 600,000. The trials which were mainly in the area of Maternal, Neonatal and Child Health were conducted by the Kintampo Health Research Centre (KHRC) in collaboration with the London School of Hygiene and Tropical Medicine (LSHTM).

Methods

The four core strategies which were used were formative research methods, the formation of the Information, Education and Communication (IEC) team to serve as the main link between the research team and the community, recruitment of field workers from the communities within which they lived, and close collaboration with national and regional stakeholders.

Results

These measures allowed trust to be built between the community members and the research team and ensured that potential misconceptions which came up in the communities were promptly dealt with through the IEC team. The decision to place field workers in the communities from which they came and their knowledge of the local language created trust between the research team and the community. The close working relationship between the District health authorities and the Kintampo Health Research Centre supported the acceptance of the research in the communities as the District Health Authorities were respected and trusted.

Conclusion

The successes achieved during the past 2 decades of collaboration between LSHTM and KHRC in conducting community-based field trials were based on involving the community in research projects. Community participation and engagement helped not only to identify the pertinent issues, but also enabled the communities and research team to contribute towards efforts to address challenges.
Evaluation of a treatment planning system developed for clinical boron neutron capture therapy and validation against an independent Monte Carlo dose calculation system
Authors: Hu Naonori , Tanaka Hiroki , Kakino Ryo , Yoshikawa Syuushi , Miyao Mamoru , Akita Kazuhiko , Isohashi Kayako , Aihara Teruhito , Nihei Keiji , Ono Koji
Published: December 2021

Boron neutron capture therapy (BNCT) for the treatment of unresectable, locally advanced, and recurrent carcinoma of the head and neck cancer has been approved by the Japanese government for reimbursement under the national health insurance as of June 2020. A new treatment planning system for clinical BNCT has been developed by Sumitomo Heavy Industries, Ltd. (Sumitomo), NeuCure® Dose Engine. To safely implement this system for clinical use, the simulated neutron flux and gamma ray dose rate inside a water phantom was compared against experimental measurements. Furthermore, to validate and verify the new planning system, the dose distribution inside an anthropomorphic head phantom was compared against a BNCT treatment planning system SERA and an in-house developed Monte Carlo dose calculation program. The simulated results closely matched the experimental results, within 5% for the thermal neutron flux and 10% for the gamma ray dose rate. The dose distribution inside the head phantom closely matched with SERA and the in-house developed dose calculation program, within 3% for the tumour and a difference of 0.3 Gyw for the brain.
Patient understanding regarding opioid use in an orthopaedic trauma surgery population: a survey study
Authors: Xu Amy L. , Dunham Alexandra M. , Enumah Zachary O. , Humbyrd Casey J.
Published: December 2021

Background

Prior studies have assessed provider knowledge and factors associated with opioid misuse; similar studies evaluating patient knowledge are lacking. The purpose of this study was to assess the degree of understanding regarding opioid use in orthopaedic trauma patients. We also sought to determine the demographic factors and clinical and personal experiences associated with level of understanding.

Methods

One hundred and sixty-six adult orthopaedic trauma surgery patients across two clinical sites of an academic institution participated in an internet-based survey (2352 invited, 7.1% response rate). Demographic, clinical, and personal experience variables, as well as perceptions surrounding opioid use were collected. Relationships between patient characteristics and opioid perceptions were identified using univariate and multivariable logistic regressions. Alpha = 0.05.

Results

Excellent recognition (> 85% correct) of common opioids, side effects, withdrawal symptoms, and disposal methods was demonstrated by 29%, 10%, 30%, and 2.4% of patients; poor recognition (< 55%) by 11%, 56%, 33%, and 52% of patients, respectively. Compared with white patients, non-white patients had 7.8 times greater odds (95% confidence interval [CI] 1.9–31) of perceiving addiction discrepancy (p = 0.004). Employed patients with higher education levels were less likely to have excellent understanding of side effects (adjusted odds ratio [aOR] 0.06, 95% CI 0.006–0.56; p = 0.01) and to understand that dependence can occur within 2 weeks (aOR 0.28, 95% CI 0.09–0.86; p = 0.03) than unemployed patients. Patients in the second least disadvantaged ADI quartile were more knowledgeable about side effects (aOR 8.8, 95% CI 1.7–46) and withdrawal symptoms (aOR 2.7, 95% CI 1.0–7.2; p = 0.046) than those in the least disadvantaged quartile. Patients who knew someone who was dependent or overdosed on opioids were less likely to perceive addiction discrepancy (aOR 0.24, 95% CI 0.07–0.76; p = 0.02) as well as more likely to have excellent knowledge of withdrawal symptoms (aOR 2.6, 95% CI 1.1–6.5, p = 0.03) and to understand that dependence can develop within 2 weeks (aOR 3.8, 95% CI 1.5–9.8, p = 0.005).

Conclusions

Level of understanding regarding opioid use is low among orthopaedic trauma surgery patients. Clinical and personal experiences with opioids, in addition to demographics, should be emphasized in the clinical history.
The degradation of Rap1GAP via E6AP-mediated ubiquitin-proteasome pathway is associated with HPV16/18-infection in cervical cancer cells
Authors: Wang Yinghui , Xie Yihang , Sun Boxuan , Guo Yuwei , Song Ling , Mohammednur Dawit Eman , Zhao Chunyan
Published: December 2021

Background

Cervical cancers are closely associated with persistent high-risk human papillomaviruses (HR HPV) infection. The main mechanism involves the targeting of tumor suppressors, such as p53 and pRB, for degradation by HR HPV-encoded oncoproteins, thereby leading to tumorigenesis. Rap1GAP, a tumor suppressor gene, is down-regulated in many cancers. Previous studies have revealed that down-regulation of Rap1GAP is correlated with HPV16/18 infection in cervical cancer. However, the molecular mechanism remains unclear. In this study, we aimed to address the degradation pathway of Rap1GAP in HPV-positive cervical cancer cells.

Methods

HPV-positive (HeLa and SiHa) and negative (C33A) cervical cancer cells were used to analyze the pathways of Rap1GAP degradation. MG132 (carbobenzoxy-leucyl-leucyl-leucine) was used to inhibit protein degradation by proteasome. Co-immunoprecipitation (co-IP) was used to detect the interaction between Rap1GAP and E6AP. siRNA for E6AP was used to silence the expression of E6AP. Rapamycin was used to induce cell autophagy. Western blotting was used to check the levels of proteins.

Results

Following treatment with MG132, the levels of Rap1GAP were increased in the HR HPV-positive HeLa and SiHa cells, but not in the HPV-negative C33A cells. Co-immunoprecipitation assay revealed ubiquitinated Rap1GAP protein in HeLa and SiHa cells, but not in C33A cells. E6-associated protein (E6AP) mediated the ubiquitination of Rap1GAP by binding to it in HeLa and SiHa cells, but not in C33A cells. However, the levels of Rap1GAP were decreased in HeLa and SiHa cells after knocking down E6AP by siRNA. Silencing of E6AP did not affect the levels of Rap1GAP in C33A cells. Autophagy marker p62 was decreased and LC3 II/LC3 I was increased after knocking down E6AP in HeLa cells, but not in C33A cells. The levels of Rap1GAP were decreased after treating the cells with rapamycin to induce cell autophagy in HeLa and C33A cells.

Conclusion

Rap1GAP may be degraded by autophagy in cervical cancer cells, but HPV infection can switch the degradation pathway from autophagy to E6AP-mediated ubiquitin-proteasome degradation. E6AP may be a key component of the switch.
Retraction Note: MNAT1 is overexpressed in colorectal cancer and mediates p53 ubiquitin-degradation to promote colorectal cancer malignance
Authors: Zhou Shan , Lu Jinping , Li Yuejin , Chen Chan , Cai Yongqiang , Tan Gongjun , Peng Zhengke , Zhang Zhenlin , Dong Zigang , Kang Tiebang , Tang Faqing
Published: December 2021

This article has been retracted. Please see the Retraction Notice for more detail: 10.1186/s13046-021-02204-1