bluuebunny/crossref_metadata_2025 huggingface dataset:
Time trend prediction and spatial–temporal analysis of multidrug-resistant tuberculosis in Guizhou Province, China, during 2014–2020
Authors: Yun Wang , Huijuan Chen , Long Liao , Xiaolong Lu , Aihua Zhang
Published: June 2022

Background

Guizhou is located in the southwest of China with high multidrug-resistant tuberculosis (MDR-TB) epidemic. To fight this disease, Guizhou provincial authorities have made efforts to establish MDR-TB service system and perform the strategies for active case finding since 2014. The expanded case finding starting from 2019 and COVID-19 pandemic may affect the cases distribution. Thus, this study aims to analyze MDR-TB epidemic status from 2014 to 2020 for the first time in Guizhou in order to guide control strategies.

Methods

Data of notified MDR-TB cases were extracted from the National TB Surveillance System correspond to population information for each county of Guizhou from 2014 to 2020. The percentage change was calculated to quantify the change of cases from 2014 to 2020. Time trend and seasonality of case series were analyzed by a seasonal autoregressive integrated moving average (SARIMA) model. Spatial–temporal distribution at county-level was explored by spatial autocorrelation analysis and spatial–temporal scan statistic.

Results

Guizhou has 9 prefectures and 88 counties. In this study, 1,666 notified MDR-TB cases were included from 2014–2020. The number of cases increased yearly. Between 2014 and 2019, the percentage increase ranged from 6.7 to 21.0%. From 2019 to 2020, the percentage increase was 62.1%. The seasonal trend illustrated that most cases were observed during the autumn with the trough in February. Only in 2020, a peak admission was observed in June. This may be caused by COVID-19 pandemic restrictions being lifted until May 2020. The spatial–temporal heterogeneity revealed that over the years, most MDR-TB cases stably aggregated over four prefectures in the northwest, covering Bijie, Guiyang, Liupanshui and Zunyi. Three prefectures (Anshun, Tongren and Qiandongnan) only exhibited case clusters in 2020.

Conclusion

This study identified the upward trend with seasonality and spatial−temporal clusters of MDR-TB cases in Guizhou from 2014 to 2020. The fast rising of cases and different distribution from the past in 2020 were affected by the expanded case finding from 2019 and COVID-19. The results suggest that control efforts should target at high-risk periods and areas by prioritizing resources allocation to increase cases detection capacity and better access to treatment.
Linking unfolded protein response to ovarian cancer cell fusion
Authors: Yart Lucile , Bastida-Ruiz Daniel , Allard Mathilde , Dietrich Pierre-Yves , Petignat Patrick , Cohen Marie
Published: June 2022

Background

Polyploid giant cancer cells (PGCCs) have been observed in epithelial ovarian tumors. They can resist antimitotic drugs, thus participating in tumor maintenance and recurrence. Although their origin remains unclear, PGCC formation seems to be enhanced by conditions that trigger the unfolded protein response (UPR) such as hypoxia or chemotherapeutic drugs like paclitaxel. Hypoxia has been shown to promote the formation of ovarian PGCCs by cell fusion. We thus hypothesized that the UPR could be involved in EOC cell fusion, possibly explaining the occurrence of PGCCs and the aggressiveness of EOC.

Methods

The UPR was induced in two ovarian cancer cell lines (SKOV3 and COV318). The UPR activation was assessed by Western blot and polyploidy indexes were calculated. Then, to confirm the implication of cell fusion in PGCC formation, two populations of SKOV3 cells were transfected with plasmids encoding for two distinct nuclear fluorescent proteins (GFP and mCherry) associated with different antibiotic resistance genes, and the two cell populations were mixed in co-culture. The co-culture was submitted to a double-antibiotic selection. The resulting cell population was characterized for its morphology, cyclicity, and proliferative and tumorigenic capacities, in addition to transcriptomic characterization.

Results

We demonstrated that cell fusion could be involved in the generation of ovarian PGCCs and this process was promoted by paclitaxel and the UPR activation. Double-antibiotic treatment of PGCCs led to the selection of a pure population of cells containing both GFP- and mCherry-positive nuclei. Interestingly, after 3 weeks of selection, we observed that these cells were no longer polynucleated but displayed a single nucleus positive for both fluorescent proteins, suggesting that genetic material mixing had occurred. These cells had reinitiated their normal cell cycles, acquired an increased invasive capacity, and could form ovarian tumorsin ovo.

Conclusions

The UPR activation increased the in vitro formation of PGCCs by cell fusion, with the newly generated cells further acquiring new properties. The UPR modulation in ovarian cancer patients could represent an interesting therapeutic strategy to avoid the formation of PGCCs and therefore limit cancer relapse and drug resistance.
Classifying and characterizing the development of self-reported overall quality of life among the Chinese elderly: a twelve-year longitudinal study
Authors: Huang Xitong , Zhang Minqiang , Fang Junyan , Zeng Qing , Wang Jinqing , Li Jia
Published: June 2022

Background

To promote healthy aging, the information about the development of quality of life (QoL) is of great importance. However, the explorations of the heterogeneity in the change of QoL under the Chinese context were limited. This study aimed to identify potential different development patterns of QoL and the influential factors using a longitudinal, nationally representative sample of the Chinese elderly.

Methods

We adopted a five-wave longitudinal dataset from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), and a total of 1645 elderly were obtained. The sample had a mean age of 72.7 years (SD = 6.64) and was 47.2% male. Overall QoL was measured through self-report during the longitudinal process. We utilized the conditional growth mixture model (GMM) with time-invariant covariates (TICs) to explore various development patterns and associated factors.

Results

Three distinct trajectories of self-reported overall QoL were identified: the High-level Steady Group (17.08%), the Mid-level Steady Group (63.10%), and the Low-level Growth Group (19.82%). Results also indicated that several factors predicted distinct trajectories of self-reported overall QoL. Those elderly who received enough financial resources, had adequate nutrition, did not exhibit any disability, engaged in leisure activities, and did less physical labor or housework at the baseline were more likely to report a higher level of overall QoL over time.

Conclusions

There existed three development patterns of self-reported overall QoL in elders, and the findings provided valuable implications for the maintenance and improvement of QoL among the Chinese elderly. Future studies could examine the influence of other confounding factors.
Instruments to measure e-cigarette related constructs: a systematic review
Authors: Park Eunhee , Kwon Misol , Chacko Thomas , Zhou Yanjun , Chen Chiahui , Goniewicz Maciej L. , Li Chin-Shang , Chang Yu-Ping
Published: June 2022

Background

Electronic cigarettes (e-cigarettes) are relatively new tobacco products that are attracting public attention due to their unique features, especially their many flavor options and their potential as an alternative to cigarettes. However, uncertainties remain regarding the determinants and consequences of e-cigarette use because current research on e-cigarettes is made more difficult due to the lack of psychometrically sound instruments that measure e-cigarette related constructs. This systematic review therefore seeks to identify the instruments in the field that are designed to assess various aspects of e-cigarette use or its related constructs and analyze the evidence presented regarding the psychometric properties of the identified instruments.

Methods

This systematic review utilized six search engines: PubMed, Medline, CINAHL, PsycINFO, Web of Science, and EMBASE, to identify articles published in the peer-reviewed journals from inception to February 2022 that contained development or validation processes for these instruments.

Results

Eighteen articles describing the development or validation of 22 unique instruments were identified. Beliefs, perceptions, motives, e-cigarette use, and dependence, were the most commonly assessed e-cigarette related constructs. The included studies reported either construct or criterion validity, with 14 studies reporting both. Most studies did not report the content validity; for reliability, most reported internal consistencies using Cronbach’s alpha, with 15 instruments reporting Cronbach’s alpha > 0.70 for the scale or its subscales.

Conclusions

Twenty-two instruments with a reported development or validation process to measure e-cigarette related constructs are currently available for practitioners and researchers.

This review provides a guide for practitioners and researchers seeking to identify the most appropriate existing instruments on e-cigarette use based on the constructs examined, target population, psychometric properties, and instrument length. The gaps identified in the existing e-cigarette related instruments indicate that future studies should seek to extend the validity of the instruments for diverse populations, including adolescents. Instruments that explore additional aspects of e-cigarette use and e-cigarette related constructs to help build a strong theoretical background and expand our current understanding of e-cigarette use and its related constructs, should also be developed.
Less meat in the shopping basket. The effect on meat purchases of higher prices, an information nudge and the combination: a randomised controlled trial
Authors: Vellinga R. E. , Eykelenboom M. , Olthof M. R. , Steenhuis I. H. M. , de Jonge R. , Temme E. H. M.
Published: June 2022

Background

Reduced meat consumption benefits human and planetary health. Modelling studies have demonstrated the significant health and environmental gains that could be achieved through fiscal measures targeting meat. Adding other interventions may enhance the effect of a fiscal measure. The current study aimed to examine the effect of higher meat prices, an information nudge and a combination of both measures on meat purchases in a three-dimensional virtual supermarket.

Methods

A parallel designed randomised controlled trial with four conditions was performed. Participants (≥ 18 years) were randomly assigned to the control condition or one of the experimental conditions: a 30% price increase for meat (‘Price condition’), an information nudge about the environmental impact of meat production and consumers’ role in that regard (‘Information nudge condition’) or a combination of both (‘Combination condition’). Participants were asked to shop for their household for one week. The primary outcome was the difference in the total amount of meat purchased in grams per household per week.

Results

Between 22 June 2020 and 28 August 2020, participants were recruited and randomly assigned to the control and experimental conditions. The final sample included 533 participants. In the ‘Combination condition’, − 386 g (95% CI: − 579, − 193) meat was purchased compared with the ‘Control condition’. Compared to the ‘Control condition’ less meat was purchased in the ‘Price condition’ (− 144 g (95%CI: − 331, 43)), although not statistically significant, whereas a similar amount of meat was purchased in the ‘Information nudge condition’ (1 g (95%CI: − 188, 189)).

Conclusion

Achieving the most pronounced effects on reduced meat purchases will require a policy mixture of pricing and an information nudge. Less meat is purchased in a virtual supermarket after raising the meat price by 30% combined with an information nudge. The results could be used to design evidence-based policy measures to reduce meat purchases.

Trial registration

The trial was registered in the Netherlands Trial Register identifier NL8628. Registered on 18/05/2020. ICTRP Search Portal (who.int) NTR (trialregister.nl).
Primary care consultations and pain medicine prescriptions: a comparison between patients with and without chronic pain after total knee replacement
Authors: Pinedo-Villanueva Rafael , Kolovos Spyros , Maronga Christopher , Delmestri Antonella , Howells Nick , Judge Andrew , Gooberman-Hill Rachael , Wylde Vikki
Published: June 2022

Background

Approximately 20% of patients experience chronic pain after total knee replacement (TKR). The impact of chronic pain after TKR on primary care services in the UK is currently unknown. The aim of this study was to compare primary care consultations and pain medicine prescriptions between patients with and without chronic pain after TKR.

Methods

Data from 5,055 patients who received TKR between 2009 and 2016 with anonymised linked data from the Clinical Practice Research Datalink Gold (CPRD) and English Hospital Episode Statistics (HES) Patient Reported Outcome Measures (PROMs) programme were analysed. The exposure time was from 10 years pre-operative to eight years post-operative. Patients with a score ≤ 14 on the Oxford Knee Score pain component scale at 6 months post-operative were classified as having chronic pain after TKR. Primary care consultations and prescribed pain medicines were quantified, and costs calculated based on national cost data.

Results

721 patients (14%) had chronic pain after TKR. The prevalence and costs of primary care consultations and pain medicine prescriptions per year were consistently higher for patients with chronic pain after TKR compared with those without chronic pain after TKR; these differences were observed both before and after surgery. There was a substantial and sustained increase in the cost of opioid prescriptions after surgery for patients with chronic pain after TKR, peaking at seven years post-operative.

Conclusions

Increased primary care consultations and pain medicine prescriptions associated with chronic pain after TKR represent a considerable financial cost to primary care services. Evaluation of interventions to reduce the risk of developing this pain condition and improve the early management of pain after TKR are needed to improve outcomes for patients and reduce costs to healthcare services.
Hand-assisted laparoscopic resection versus total laparoscopic gastric surgery for primary gastric gastrointestinal stromal tumors (GISTs): an analysis from a high-volume institution
Authors: Zhao Ya-Jun , Qiu Yong-Qiang , Zhong Li-Ying , Zheng Wen-Ze , Zhuang Lv-Ping , Wei Zhong , Ning Zhong-Liang
Published: June 2022

Background

Laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) is technically feasible and associated with favorable outcomes. We compared the clinical efficacy of hand-assisted laparoscopic surgery (HLS) and total laparoscopic surgery (TLS) for gastric GISTs.

Methods

We retrospectively analyzed the clinical data of 69 consecutive patients diagnosed with a gastric GIST in a tertiary referral teaching hospital from December 2016 to December 2020. Surgical outcomes were compared between two groups.

Results

Fifty-three patients (TLS group: n = 36; HLS group: n = 17) were included. The mean age was 56.9 and 58.1 years in the TLS and HLS groups, respectively. The maximum tumor margin was significantly shorter in the HLS group than in the TLS group (2.3 ± 0.9. vs. 3.0 ± 0.8 cm; P = 0.004). The operative time of the HLS group was significantly shorter than that of the TLS group (70.6 ± 19.1 min vs. 134.4 ± 53.7 min; P < 0.001). The HLS group had less intraoperative blood loss, a shorter time to first flatus, and a shorter time to fluid diet than the TLS group (P < 0.05). No significant difference was found between the groups in the incidence or severity of complications within 30 days after surgery. Recurrence or metastasis occurred in four cases (HLS group; n = 1; TLS group; n = 3).

Conclusions

This study demonstrated that compared with TLS, HLS for gastric GISTs has the advantages of simpler operation, shorter operative time, and faster postoperative recovery.
Aggressiveness of care in the last days of life in the emergency department of a tertiary hospital in Korea
Authors: Kim Jung Sun , Lee Sun Young , Lee Min Sung , Yoo Shin Hye , Shin Jeongmi , Choi Wonho , Kim Yejin , Han Hyung Sook , Hong Jinui , Keam Bhumsuk , Heo Dae Seog
Published: June 2022

Background

High-quality end-of-life (EOL) care requires both comfort care and the maintenance of dignity. However, delivering EOL in the emergency department (ED) is often challenging. Therefore, we aimed to investigate characteristics of EOL care for dying patients in the ED.

Methods

We conducted a retrospective cohort study of patients who died of disease in the ED at a tertiary hospital in Korea between January 2018 and December 2020. We examined medical care within the last 24 h of life and advance care planning (ACP) status.

Results

Of all 222 disease-related mortalities, 140 (63.1%) were men, while 141 (63.5%) had cancer. The median age was 74 years. As for critical care, 61 (27.5%) patients received cardiopulmonary resuscitation, while 80 (36.0%) received mechanical ventilation. The absence of serious illness (p = 0.011) and the lack of an advance statement (p < 0.001) were both independently associated with the receipt of more critical care. Only 70 (31.5%) patients received comfort care through opioids. Younger patients (< 75 years) (p = 0.002) and those who completed life-sustaining treatment legal forms (p = 0.001) received more comfort care. While EOL discussions were initiated in 150 (67.6%) cases, the palliative care team was involved only in 29 (13.1%).

Conclusions

Patients in the ED underwent more aggressive care and less comfort care in a state of imminent death. To ensure better EOL care, physicians should minimize redundant evaluations and promptly introduce ACP.
Intimate partner violence among pregnant women in Kenya: forms, perpetrators and associations
Authors: Stiller Mariella , Bärnighausen Till , Wilson Michael Lowery
Published: June 2022

Background

Intimate Partner violence (IPV) among pregnant women is a significant problem of public health importance. Nevertheless, there are relatively few studies which have examined the phenomenon in sub-Saharan settings. The aim of this study was to provide an overview of the prevalence, perpetrators, and associated factors of IPV during pregnancy in Kenya.

Methods

We were making use of the 2014 Kenyan Demographic and Health Survey (KDHS) data and included women and girls of reproductive age (15–49 years) who have ever been pregnant ($$n=4331$$

n
=
4331

). A weighted sample of respondents who have experienced violence during pregnancy ($$n=397$$

n
=
397

) were selected for further bivariate and multivariable logistic regression analyses in order to examine the association between IPV and socio-demographic factors.

Results

The prevalence of violence among pregnant women in Kenya was 9.2%, perpetrated mostly by the current husband or partner (47.6%), followed by the former husband or partner (31.5%). Physical violence was the most common (78.6%), followed by emotional (67.8%) and sexual (34.8%). Having one or two children ($$\hbox {aOR} =0.68$$

aOR
=
0.68

; $$\hbox {CI} = 0.53{-}0.88$$

CI
=
0.53
-
0.88

), having secondary or higher education ($$\hbox {aOR} = 0.53$$

aOR
=
0.53

; $$\hbox {CI} = 0.40{-}0.69$$

CI
=
0.40
-
0.69

) and being 18 years and above at first cohabitation ($$\hbox {aOR} = 0.75$$

aOR
=
0.75

; $$\hbox {CI}= 0.60{-}0.94$$

CI
=
0.60
-
0.94

) and at sexual debut ($$\hbox {aOR} = 0.65$$

aOR
=
0.65

; $$\hbox {CI}=0.53{-}0.80$$

CI
=
0.53
-
0.80

) were significantly associated with fewer reports of violence during pregnancy. Pregnant women who were divorced, separated or widowed ($$\hbox {aOR} = 1.91$$

aOR
=
1.91

; $$\hbox {CI} =1.47{-}2.47$$

CI
=
1.47
-
2.47

), who were employed ($$\hbox {aOR} = 1.34$$

aOR
=
1.34

; $$\hbox {CI} =1.06{-}1.70$$

CI
=
1.06
-
1.70

), who had witnessed their fathers beat their mothers ($$\hbox {aOR} = 1.59$$

aOR
=
1.59

; $$\hbox {CI} = 1.28{-}1.97$$

CI
=
1.28
-
1.97

) and who had primary education ($$\hbox {aOR} = 1.53$$

aOR
=
1.53

; $$\hbox {CI} = 1.11{-}2.14$$

CI
=
1.11
-
2.14

) were significantly more likely to experience violence.

Conclusions

To prevent violence among pregnant women in Kenya, training health care providers should go hand in hand with interventions sensitising and mobilising community members, both addressing the socio-demographic drivers of IPV during pregnancy and directing a particular attention to the most vulnerable ones.
The effect of nutrition education for cancer prevention based on health belief model on nutrition knowledge, attitude, and practice of Iranian women
Authors: Sasanfar Bahareh , Toorang Fatemeh , Rostami Sahar , Yeganeh Maryam Zarif , Ghazi Maryam Lafzi , Seyyedsalehi Monireh Sadat , Zendehdel Kazem
Published: June 2022

Background

In recent years, nutrition has received an increasingly important role in the etiology of cancer. Thus, public education about dietary factors associated with cancer risk or prevention could be an important intervention for cancer prevention, particularly in low- and middle-income countries where the burden of cancer is increasing rapidly and the access to care is limited. The age-standardized incidence of breast cancer was 35.8 among Iranian women in 2020. We aimed to study the effect of nutrition education on the knowledge, attitude, and practice of Iranian women towards dietary factors related to cancer.

Methods

In this interventional study, 229 women from public health centers were recruited and underwent three 75-min sessions of education based on the Health Belief Model (HBM). Participants were interviewed by trained interviewers using a validated and reproducible nutrition-related cancer prevention knowledge, attitude, and practice questionnaire (NUTCANKAP) questionnaire designed based on the HBM. Nutritional knowledge, attitude, and practice of participants were assessed through this questionnaire. Three 24-h dietary recalls (one weekend and two nonconsecutive weekdays) were also collected before and one month after the intervention.

Results

The mean age of the participants was 45.14 years, and the mean BMI was 27.2 kg/m2. After the intervention, the participants had a higher intake of whole grain (p = 0.03) and a lower fat dairy (p = 0.009) and nuts (p = 0.04). However, the intake of high-fat dairy (p = 0.001) decreased after the intervention. We indicated significant differences in knowledge (p < 0.001) and nutritional practice scores (p = 0.01) after education. In addition, after the intervention, there were significant differences in the mean score of the HBM components, except for the perceived self-efficacy.

Conclusion

Participation in a nutrition education program positively impacted the knowledge and nutritional practices linked to cancer prevention.
Exploring culinary medicine as a promising method of nutritional education in medical school: a scoping review
Authors: Tan Jacqueline , Atamanchuk Levi , Rao Tanish , Sato Kenichi , Crowley Jennifer , Ball Lauren
Published: June 2022

Background

Dietary modifications are considered a first-line intervention for chronic disease management, yet graduating doctors still report not feeling competent to counsel patients on their diet. Research has focused on methods to address this shortfall in physician competency, including culinary medicine. Culinary medicine is an approach to education that involves hands-on food and cooking learning experiences to equip participants with tools for improving the nutrition behaviour and health of their future patients. Despite positive findings in the efficacy of these interventions, they differ markedly in approach and target, which therefore fails to provide adequate evidence that could serve to guide future culinary medicine interventions.

Objective

A scoping review to synthesize the existing literature on culinary medicine interventions that are offered during medical training.

Methods

Online databases were used to identify literature published prior to April 2022 that involve a hands-on culinary medicine component to nutrition and examine academic impact, feasibility and acceptability.

Results

Twenty-four studies met the eligibility criteria. Despite promising gains in nutrition knowledge, confidence and high acceptability of the programs, large variations exist in delivery method, setting, and course content between programs. There is a lack of program cost reporting and long-term follow up of participants, inconsistent evidence for improved nutrition attitudes amongst participants, as well as geographically limited adoption of such programs.

Conclusions

The findings of this research demonstrate a clear increase in interest in the use of hands-on culinary medicine programs as educational tools, evidence of feasibility in implementation, and improved student nutritional knowledge, skill and counseling compared to a traditional didactic curriculum. The quality of culinary medicine research studies is increasing and the aims of research are narrowing to focus on how culinary medicine can positively impact medical education. The findings from this review will aid in legitimising culinary medicine as an effective delivery method of nutritional education in medical programs.
Impact of background music on the performance of laparoscopy teams
Authors: Han Ying , Zheng Bin , Zhao Linyong , Hu Jiankun , Zhang Chao , Xiao Ran , Wang Chunyan , Pu Dan
Published: June 2022

Background

Acoustic conditions in the operating room have different impacts on surgeon’s performance. Their effects on the performance of surgical teams are not well documented. We investigated if laparoscopic teams operating under pleasant acoustic conditions would perform better than under noisy conditions.

Methods

We recruited 114 surgical residents and built 57 two-person teams. Each team was required to perform two laparoscopic tasks (object transportation and collaborative suturing) on a simulation training box under music, neutral, and noisy acoustic conditions. Data were extracted from video recordings of each performance for analysis. Task performance was measured by the duration of time to complete a task and the total number of errors, and objective performance scores. The measures were compared over the three acoustic conditions.

Results

A music environment elicited higher performance scores than a noisy environment for both the object transportation (performance score: 66.3 ± 8.6 vs. 57.6 ± 11.2; p < 0.001) and collaborative suturing tasks (78.6 ± 5.4 vs. 67.2 ± 11.1; p < 0.001). Task times in the music and noisy environments was subtracted to produce a music-noisy difference time. Pearson correlation coefficient analysis showed a significant negative relationship between the team experience score and the music-noisy difference time on the object transportation (r = − 0.246, p = 0.046) and collaborative suturing tasks (r = − 0.248, p = 0.044).

Conclusions

As to individuals, music enhances the performance of a laparoscopy team while a noisy environment worsens performance. The negative correlation between team experience and music-noisy difference time suggests that laparoscopy teams composed of experienced surgeons are less likely affected by an acoustic distraction than the noisy teams. Team resistance to acoustic distraction may lead to a new way for assessing team skills.
Oldest preserved umbilical scar reveals dinosaurs had ‘belly buttons’
Authors: Bell Phil R. , Hendrickx Christophe , Pittman Michael , Kaye Thomas G.
Published: June 2022

Background

In egg-laying amniotes, the developing embryo is tethered to a number of the extraembryonic membranes including the yolk sac and allantois that deliver oxygen and nutrients and remove metabolic waste products throughout embryonic development. Prior to, or soon after hatching, these membranes detach from the animal leaving a temporary or permanent umbilical scar (umbilicus) equivalent to the navel or ‘belly button’ in some placental mammals, including humans. Although ubiquitous in modern mammals and reptiles (including birds), at least early in their ontogeny, the umbilicus has not been identified in any pre-Cenozoic amniote.

Results

We report the oldest preserved umbilicus in a fossil amniote from a ~130-million-year-old early-branching ceratopsian dinosaur, Psittacosaurus. Under laser-stimulated fluorescence (LSF), the umbilicus is revealed as an elongate midline structure delimited by a row of paired scales on the abdomen. The relatively late ontogenetic stage (close to sexual maturity) estimated for the individual indicates that the umbilicus was probably retained throughout life.

Conclusions

Unlike most extant reptiles and birds that lose this scar within days to weeks after hatching, the umbilicus of Psittacosaurus persisted at least until sexual maturity, similar to some lizards and crocodylians with which it shares the closest morphological resemblance. This discovery is the oldest record of an amniote umbilicus and the first in a non-avian dinosaur. However, given the variability of this structure in extant reptilian analogues, a persistent umbilical scar may not have been present in all non-avian dinosaurs.
Dry season prevalence of Plasmodium falciparum in asymptomatic Gambian children, with a comparative evaluation of diagnostic methods
Authors: Mooney Jason P. , DonVito Sophia M. , Jahateh Maimuna , Bittaye Haddy , Bottomley Christian , D’Alessandro Umberto , Riley Eleanor M.
Published: June 2022

Background

Subclinical infection with Plasmodium falciparum remains highly prevalent, yet diagnosing these often low-density infections remains a challenge. Infections can be subpatent, falling below the limit of detection for conventional thick-film microscopy and rapid diagnostic testing (RDT). In this study, the prevalence of subclinical P. falciparum infections in school-aged children was characterised at the start of the dry season in the Upper River Region of The Gambia in 2017/2018, with a goal to also compare the utility of different diagnostic tools.

Methods

In a cross-sectional survey of children living in 29 villages on the south bank of the Gambia river (median age of 10 years), matched microscopy, rapid diagnostic test (RDT, detecting histidine-rich protein 2) and polymerase chain reaction (PCR, targeting either 18S rRNA or var gene acidic terminal sequence) were used to determine the prevalence of patent and subpatent infections and to compare the performance of the different diagnostic methods.

Results

The prevalence of var gene acidic terminal sequence (varATS) qPCR-detectable infections was 10.2% (141/1381) with a median density of 3.12 parasites/µL. Malaria prevalence was highly heterogeneous across the region, ranging from < 1% to ~ 40% prevalence in different village clusters. Compared to varATS, 18S rRNA PCR detected fewer low-density infections, with an assay sensitivity of 50% and specificity of 98.8%. Parasite prevalence in the cohort was 2.9% by microscopy and 1.5% by RDT. Compared to varATS qPCR, microscopy and RDT had sensitivities of 11.5% and 9.2%, respectively, although both methods were highly specific (> 98%). Samples that were positive by all three tests (varATS qPCR, RDT and microscopy) had significantly higher parasite densities (median = 1705 parasites/µL) than samples that were positive by varATS qPCR only (median = 2.4 parasites/µL).

Conclusions

The majority of subclinical malaria infections in school-aged children were of extremely low parasite density and detectable only by ultra-sensitive PCR analysis. Understanding the duration of these low density infections, their physiological impact and their contribution to sustained parasite transmission is necessary to inform malaria elimination strategies.
Expression and copper binding characteristics of Plasmodium falciparum cytochrome c oxidase assembly factor 11, Cox11
Authors: Salman Abdulmalik Abdullahi , Goldring J. P. Dean
Published: June 2022

Background

Copper is an essential metal for living organisms as a catalytic co-factor for important enzymes, like cytochrome c oxidase the final enzyme in the electron transport chain. Plasmodium falciparum parasites in infected red blood cells are killed by excess copper and development in erythrocytes is inhibited by copper chelators. Cytochrome c oxidase in yeast obtains copper for the CuB site in the Cox1 subunit from Cox11.

Methods

A 162 amino acid carboxy-terminal domain of the P. falciparum Cox11 ortholog (PfCox11Ct) was recombinantly expressed and the rMBPPfCox11Ct affinity purified. Copper binding was measured in vitro and in Escherichia coli host cells. Site directed mutagenesis was used to identify key copper binding cysteines. Antibodies confirmed the expression of the native protein.

Results

rMBPPfCox11Ct was expressed as a 62 kDa protein fused with the maltose binding protein and affinity purified. rMBPPfCox11Ct bound copper measured by: a bicinchoninic acid release assay; atomic absorption spectroscopy; a bacterial host growth inhibition assay; ascorbate oxidation inhibition and in a thermal shift assay. The cysteine 157 amino acid was shown to be important for in vitro copper binding by PfCox11whilst Cys 60 was not. The native protein was detected by antibodies against rMBPPfCox11Ct.

Conclusions

Plasmodium spp. express the PfCox11 protein which shares structural features and copper binding motifs with Cox11 from other species. PfCox11 binds copper and is, therefore, predicted to transfer copper to the CuB site of Plasmodium cytochrome c oxidase. Characterization of Plasmodium spp. proteins involved in copper metabolism will help sceintists understand the role of cytochrome c oxidase and this essential metal in Plasmodium homeostasis.
Integration of radiogenomic features for early prediction of pathological complete response in patients with triple-negative breast cancer and identification of potential therapeutic targets
Authors: Zhang Ying , You Chao , Pei Yuchen , Yang Fan , Li Daqiang , Jiang Yi-zhou , Shao Zhimin
Published: June 2022

Background

We established a radiogenomic model to predict pathological complete response (pCR) in triple-negative breast cancer (TNBC) and explored the association between high-frequency mutations and drug resistance.

Methods

From April 2018 to September 2019, 112 patients who had received neoadjuvant chemotherapy were included. We randomly split the study population into training and validation sets (2:1 ratio). Contrast-enhanced magnetic resonance imaging scans were obtained at baseline and after two cycles of treatment and were used to extract quantitative radiomic features and to construct two radiomics-only models using a light gradient boosting machine. By incorporating the variant allele frequency features obtained from baseline core tissues, a radiogenomic model was constructed to predict pCR. Additionally, we explored the association between recurrent mutations and drug resistance.

Results

The two radiomics-only models showed similar performance with AUCs of 0.71 and 0.73 (p = 0.55). The radiogenomic model had a higher predictive ability than the radiomics-only model in the validation set (p = 0.04), with a corresponding AUC of 0.87 (0.73–0.91).

Two highly frequent mutations were selected after comparing the mutation sites of pCR and non-pCR populations. The MED23 mutation p.P394H caused epirubicin resistance in vitro (p < 0.01). The expression levels of γ-H2A.X, p-ATM and p-CHK2 in MED23 p.P394H cells were significantly lower than those in wild type cells (p < 0.01). In the HR repair system, the GFP positivity rate of MED23 p.P394H cells was higher than that in wild-type cells (p < 0.01).

Conclusions

The proposed radiogenomic model has the potential to accurately predict pCR in TNBC patients. Epirubicin resistance after MED23 p.P394H mutation might be affected by HR repair through regulation of the p-ATM-γ-H2A.X-p-CHK2 pathway.
Stress-induced epinephrine promotes epithelial-to-mesenchymal transition and stemness of CRC through the CEBPB/TRIM2/P53 axis
Authors: Zhou Zili , Shu Yan , Bao Haijun , Han Shengbo , Liu Zhengyi , Zhao Ning , Yuan Wenzheng , Jian Chenxing , Shu Xiaogang
Published: June 2022

Background

Previous studies have indicated that chronic emotional stressors likely participate in the occurrence of cancers. However, direct evidence connecting stress and colorectal cancer development remains almost completely unexplored.

Methods

Chronic stress mouse model was used to investigate the influence of stress on tumorigenesis. Several major agonists and antagonists of adrenergic receptors were applied to investigate the effects of β-adrenergic signaling on the development of CRC. Chromatin immunoprecipitation assays (CHIP) were used to investigate the binding of p53 and CEBPB to TRIM2 promoter. Mammosphere cultures, Cell Counting Kit-8 (CCK-8) assay, colony-formation assay, scratch wound healing assays, qPCR, immunofluorescence, coimmunoprecipitation and western blotting were used to explore the effect of stress-induced epinephrine on the CEBPB/TRIM2/P53 axis and the progress of CRC cells.

Results

In this study, we found that stress-induced epinephrine (EPI) promotes the proliferation, metastasis and CSC generation of CRC primarily through the β2-adrenergic receptor. Furthermore, our studies also confirmed that chronic stress decreased the stability of p53 protein by promoting p53 ubiquitination. Results of transcriptome sequencing indicated that TRIM2 was overexpressed in cells treated with EPI. Further studies indicated that TRIM2 could regulate the stability of p53 protein by promoting p53 ubiquitination. Finally, we further proved that CEBPB was regulated by EPI and acts as the upstream transcription factor of TRIM2.

Conclusions

Our studies proved that stress-induced EPI promotes the development and stemness of CRC through the CEBPB/TRIM2/P53 axis.
TMEM16A as a potential treatment target for head and neck cancer
Authors: Okuyama Kohei , Yanamoto Souichi
Published: June 2022

Transmembrane protein 16A (TMEM16A) forms a plasma membrane-localized Ca2+-activated Cl- channel. Its gene has been mapped to an area on chromosome 11q13, which is amplified in head and neck squamous cell carcinoma (HNSCC). In HNSCC, TMEM16A overexpression is associated with not only high tumor grade, metastasis, low survival, and poor prognosis, but also deterioration of clinical outcomes following platinum-based chemotherapy. Recent study revealed the interaction between TMEM16A and transforming growth factor-β (TGF-β) has an indirect crosstalk in clarifying the mechanism of TMEM16A-induced epithelial-mesenchymal transition. Moreover, human papillomavirus (HPV) infection can modulate TMEM16A expression along with epidermal growth factor receptor (EGFR), whose phosphorylation has been reported as a potential co-biomarker of HPV-positive cancers. Considering that EGFR forms a functional complex with TMEM16A and is a co-biomarker of HPV, there may be crosstalk between TMEM16A expression and HPV-induced HNSCC. EGFR activation can induce programmed death ligand 1 (PD-L1) synthesis via activation of the nuclear factor kappa B pathway and JAK/STAT3 pathway. Here, we describe an interplay among EGFR, PD-L1, and TMEM16A. Combination therapy using TMEM16A and PD-L1 inhibitors may improve the survival rate of HNSCC patients, especially those resistant to anti-EGFR inhibitor treatment. To the best of our knowledge, this is the first review to propose a biological validation that combines immune checkpoint inhibition with TMEM16A inhibition.
In-silico and in-vitro studies on the efficacy of mangiferin against colorectal cancer
Authors: Samadarsi Rohini , Augustin Linus , Kumar Chandan , Dutta Debjani
Published: June 2022

Background

Mangiferin is a C-glycoside xanthone molecule having a wide range of therapeutic properties. Hence, the present study aims to understand the efficacy of mangiferin against colorectal cancer (CRC) and to elucidate the mechanisms of action of mangiferin on colorectal cancer.

Method

The molecular mechanism of mangiferin against colorectal cancer was studied using Autodock Vina software. Pharmacophore analysis of mangiferin concerning five COX-2 inhibitor drugs was carried out using the PharmaGist server to analyze the possibility of using mangiferin as a COX-2 inhibitor. In vitro analysis of Mangiferin against various cancer cell lines was performed.

Results

The molecular mechanism of action of mangiferin against CRC was assessed by docking with multiple target proteins involved in the progression of CRC. Docking studies showed good binding scores (kcal/mol) ranging from − 10.3 to − 6.7. Mangiferin showed a good affinity towards enzymes like COX-2 and LA4H involved in Arachidonic acid (AA) metabolism with a binding score(kcal/mol) of − 10.1 and − 10.3 respectively. The pharmacophore feature assessment of mangiferin was done for COX-2 inhibitor drugs, which further confirmed that mangiferin poses the same pharmacophore feature as that of COX-2 inhibitor drugs. Furthermore, the binding affinity of mangiferin was compared with five COX-2 inhibitor drugs to prove its efficacy as an inhibitor. Mangiferin also had a cytotoxic effect against colorectal cancer (HT 29), cervical cancer (HeLa), and breast cancer (MCF 7) cell lines. The study could establish that Mangiferin might be a promising candidate for the treatment of colorectal cancer.

Conclusion

In short, these studies exploited the possibility of mangiferin as a lead molecule to develop anticancer/anti-inflammatory drugs for the treatment of CRC.
Diversity of Borrelia burgdorferi sensu lato in ticks and small mammals from different habitats
Authors: Król Nina , Obiegala Anna , Imholt Christian , Arz Charlotte , Schmidt Elisabeth , Jeske Kathrin , Ulrich Rainer Günter , Rentería‑Solís Zaida , Jacob Jens , Pfeffer Martin
Published: June 2022

Background

Ixodid ticks are important vectors for zoonotic pathogens, with Ixodes ricinus being the most important in Europe. Rodents are hosts of immature life stages of I. ricinus ticks and are considered main reservoirs for tick-borne pathogens, e.g. Borrelia burgdorferi. The aim of this study was to analyse the prevalence as well as genospecies and sequence type (ST) diversity of Borrelia burgdorferi sensu lato in ticks and small mammals from central Germany and to elaborate on the influence of environmental and/or individual host and vector factors on Borrelia prevalence.

Methods

After species identification, 1167 small mammal skin samples and 1094 ticks from vegetation were screened by B. burgdorferi sensu lato real-time polymerase chain reaction, and positive samples were characterized by multilocus sequence typing. Generalized linear (mixed) models were used to estimate how seasonality, small mammal species/tick life stage and habitat affect individual infection status.

Results

In total, 10 small mammal species and three tick species, Ixodes ricinus, Ixodes inopinatus (both considered members of the I. ricinus complex) and Dermacentor reticulatus, were investigated. Borrelia DNA was detected in eight host species, i.e. the striped field mouse (Apodemus agrarius), the yellow-necked field mouse (Apodemus flavicollis), the wood mouse (Apodemus sylvaticus), the water vole (Arvicola amphibius), the bank vole (Clethrionomys glareolus), the field vole (Microtus agrestis), the common vole (Microtus arvalis), and the common shrew (Sorex araneus). Two species were Borrelia negative, the greater white-toothed shrew (Crocidura russula) and the pygmy shrew (Sorex minutus). The average prevalence was 6.2%, with two genospecies detected, Borrelia afzelii and Borrelia garinii, and at least three STs that had not been previously reported in small mammals. Borrelia prevalence in small mammals did not differ between seasons. Six genospecies of Borrelia—Borrelia afzelii, Borrelia valaisiana, Borrelia garinii, Borrelia lusitaniae, Borrelia spielmanii, and Borrelia burgdorferi sensu stricto—and 25 STs of Borrelia, of which 12 have not been previously described at all and five have not been previously reported in Germany, were detected in 13% of I. ricinus complex ticks. Prevalence was highest in adult females (25.3%) and lowest in nymphs (11.4%). Prevalence was significantly higher in ticks from grassland (16.8%) compared to forests (11.4%).

Conclusions

The high level of small mammal diversity in this region of Germany seems to be reflected in a wide variety of genospecies and STs of B. burgdorferi.

Graphical abstract
Toll like receptor 4 gene Asp299Gly polymorphism increases the risk of diabetic microvascular complications: a meta analysis
Authors: Zhang Yuqi , Li Huanhuan , Wang Chenyi , Lv Haihong , Fu Songbo
Published: June 2022

Objective

The relationship between Toll like receptor 4(TLR4) gene Asp299Gly polymorphism and diabetic microvascular complications (DMI) is unclear. Therefore, the aim of this meta analysis was to explore the relationship between TLR4 Asp299Gly polymorphism and DMI.

Methods

System search PubMed, Web of science, Springer, Cochrane library, ELSEVIER, Wanfang database, VIP, CNKI, a case–control study of the correlation between TLR4 gene Asp299Gly polymorphism and DMI published before June 2020 was collected.

Results

We included 6 articles, a total of 11 studies involving patients with type 2 diabetes mellitus (T2DM) complicated by microvascular complications 1834 cases, without corresponding microvascular complications 4069 cases. TLR4 gene Asp299Gly polymorphism increased the risk of microvascular complications in T2DM (dominant model OR = 1.52, 95% CI 1.10–2.09, p = 0.01; allelic model OR = 1.42, 95% CI 1.02–1.96, p = 0.04). Subgroup analysis by race and different type of microvascular complications, we found that TLR4 gene Asp299Gly polymorphism was associated with increased risk of microvascular complications in the Caucasian population (dominant model OR = 1.69, 95% CI 1.22–2.35, P = 0.002; allelic model OR = 1.56, 95% CI 1.10–2.21, P = 0.01) and increased the risk of retinopathy in patients with T2DM(dominant model OR = 1.81, 95% CI 1.04–3.14, P = 0.03; allelic model OR = 1.77, 95% CI 1.05–2.98, P = 0.03).

Conclusion

TLR4 gene Asp299Gly polymorphism was associated with increased risk of microvascular complications in patients with T2DM, especially diabetic retinopathy (DR).
A systematic review and meta-analysis on the differentiation of glioma grade and mutational status by use of perfusion-based magnetic resonance imaging
Authors: van Santwijk Lusien , Kouwenberg Valentina , Meijer Frederick , Smits Marion , Henssen Dylan
Published: June 2022

Background

Molecular characterization plays a crucial role in glioma classification which impacts treatment strategy and patient outcome. Dynamic susceptibility contrast (DSC) and dynamic contrast enhanced (DCE) perfusion imaging have been suggested as methods to help characterize glioma in a non-invasive fashion. This study set out to review and meta-analyze the evidence on the accuracy of DSC and/or DCE perfusion MRI in predicting IDH genotype and 1p/19q integrity status.

Methods

After systematic literature search on Medline, EMBASE, Web of Science and the Cochrane Library, a qualitative meta-synthesis and quantitative meta-analysis were conducted. Meta-analysis was carried out on aggregated AUC data for different perfusion metrics.

Results

Of 680 papers, twelve were included for the qualitative meta-synthesis, totaling 1384 patients. It was observed that CBV, ktrans, Ve and Vp values were, in general, significantly higher in IDH wildtype compared to IDH mutated glioma. Meta-analysis comprising of five papers (totaling 316 patients) showed that the AUC of CBV, ktrans, Ve and Vp were 0.85 (95%-CI 0.75–0.93), 0.81 (95%-CI 0.74–0.89), 0.84 (95%-CI 0.71–0.97) and 0.76 (95%-CI 0.61–0.90), respectively. No conclusive data on the prediction of 1p/19q integrity was available from these studies.

Conclusions

Future research should aim to predict 1p/19q integrity based on perfusion MRI data. Additionally, correlations with other clinically relevant outcomes should be further investigated, including patient stratification for treatment and overall survival.