bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of autistic traits on response to and side-effects of pharmacological ADHD treatment in children with ADHD: results from a prospective clinical cohort
Authors: Lilja Maria M. , Sandblom Emil , Lichtenstein Paul , Serlachius Eva , Hellner Clara , Bhagia Jyoti , Halldner Linda
Published: March 2022

Background

Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition that globally affects an average of around 5% of children and is associated with several adverse life outcomes. Comorbidity with autism spectrum disorder (ASD) is highly prevalent. Pharmacological treatment for ADHD symptoms has been shown to be effective. However, the prevailing perception is that children with ADHD and concomitant ASD symptoms report poorer efficacy and more side effects. This has been supported by studies on this population, but prospective studies directly comparing children with ADHD and different levels of ASD symptoms are lacking. We aimed to assess if children with ADHD and concomitant ASD symptoms differ regarding effects and side-effects of pharmacological ADHD treatment compared to children with ADHD without ASD traits. This is to our knowledge the second study to directly compare the effect of ADHD medication between ADHD patients with different levels of ASD symptoms.

Methods

In a non-randomized, observational, prospective cohort study, 323 patients aged 6 to 17 years who were diagnosed with ADHD and starting pharmacological treatment were divided into two groups: one with high level of ASD symptoms (ASD group, N=71) and one with low level of ASD symptoms (non-ASD group, N = 252). Treatment outcome was measured as ADHD symptoms, and evaluated using the Swanson, Nolan and Pelham Teacher and Parent ADHD rating scale-version IV (SNAP-IV). Side-effects were evaluated using the Pediatric Side Effects Checklist (P-SEC), at 3 months follow-up.

Results

From baseline to 3 months, there was no significant difference in neither treatment effect nor number of clinically significant adverse events experienced between the ASD group and the non-ASD group.

Conclusions

Our results did not implicate that ADHD patients with concomitant ASD symptoms have decreased treatment effect of ADHD medication than patients with ADHD without concomitant ASD symptoms. Neither did the results support that ADHD patients with ASD symptoms experienced significantly more side-effects than ADHD patients without ASD symptoms. Although, we did not analyze different medications separately, this is in line with the only previous study directly comparing methylphenidate treatment in children with or without ASD.

Trial registration

NCT02136147, May 12, 2014.
Hyaluronan self-agglomerating nanoparticles for non-small cell lung cancer targeting
Authors: Kim Joo-Eun , Park Young-Joon
Published: March 2022

Background

Owing to the limited amount of research, there are no nanoparticle-based anticancer agents that use hydrophilic drugs. Therefore, we developed irinotecan-loaded self-agglomerating hyaluronan nanoparticles (ISHNs). While irinotecan has high hydrophilicity, the resulting nanoparticle should possess high anticancer drug-loading capacity and allow selective targeting of the cluster of differentiation 44 (CD44) protein, which is overexpressed on the surface of tumor cells.

Results

The ISHNs were successfully made with hyaluronan (HA) as a targeting moiety, FeCl3 as a binder, and D-glutamic acid (GA) as a stabilizer. The ISHNs self-agglomerated via chelating bonding and were lyophilized using a freeze dryer. The particle diameter and zeta potential of the ISHNs were 93.8 ± 4.48 nm and − 36.3 ± 0.28 mV, respectively; a relatively narrow size distribution was observed. The drug fixation yield and drug-loading concentration were 58.3% and 1.75 mg/mL, respectively. Affinity studies revealed a tenfold stronger targeting to H23 (CD44+) non-small-cell lung cancer (NSCLC) cells, than of A549 (CD44−) cells.

Conclusion

We developed irinotecan-loaded ISHNs, which comprised irinotecan hydrochloride as a water-soluble anticancer agent, HA as a targeting moiety, FeCl3 as a binder for self-agglomeration, and GA as a stabilizer; HA is a binding material for CD44 in NSCLC cells. Owing to their ease of manufacture, excellent stability, non-cell toxicity and CD44-targeting ability, ISHNs are potential nanocarriers for passive and active tumor targeting.
Ethylene-induced potassium transporter AcKUP2 gene is involved in kiwifruit postharvest ripening
Authors: Shan Nan , Zhang Yupei , Xu Yunhe , Yuan Xin , Wan Chunpeng , Chen Chuying , Chen Jinyin , Gan Zengyu
Published: March 2022

Background

Potassium (K) is important in the regulation of plant growth and development. It is the most abundant mineral element in kiwifruit, and its content increases during fruit ripening. However, how K+ transporter works in kiwifruit postharvest maturation is not yet clear.

Results

Here, 12 K+ transporter KT/HAK/KUP genes, AcKUP1 ~ AcKUP12, were isolated from kiwifruit, and their phylogeny, genomic structure, chromosomal location, protein properties, conserved motifs and cis-acting elements were analysed. Transcription analysis revealed that AcKUP2 expression increased rapidly and was maintained at a high level during postharvest maturation, consistent with the trend of K content; AcKUP2 expression was induced by ethylene, suggesting that AcKUP2 might play a role in ripening. Fluorescence microscopy showed that AcKUP2 is localised in the plasma membrane. Cis-elements, including DER or ethylene response element (ERE) responsive to ethylene, were found in the AcKUP2 promoter sequence, and ethylene significantly enhanced the AcKUP2 promoter activity. Furthermore, we verified that AcERF15, an ethylene response factor, directly binds to the AcKUP2 promoter to promote its expression. Thus, AcKUP2 may be an important potassium transporter gene which involved in ethylene-regulated kiwifruit postharvest ripening.

Conclusions

Therefore, our study establishes the first genome-wide analysis of the kiwifruit KT/HAK/KUP gene family and provides valuable information for understanding the function of the KT/HAK/KUP genes in kiwifruit postharvest ripening.
Decreased triiodothyronine (T3) as a predictor for prolonged mechanical ventilation in critically ill patients with cardiac surgery
Authors: Shen Xiao , Sun Jiakui , Hong Liang , Song Xiaochun , Zhang Cui , Liu Ying , Liu Han , Li Guojian , Mu Xinwei
Published: March 2022

Background

This study aimed to examine the correlation between thyroid hormone and prolonged mechanical ventilation (MV) in adult critically ill patients having undergone cardiac surgery.

Methods

The present study refers to a retrospective, cohort study conducted at Nanjing First Hospital from March 2019 to December 2020. Patients receiving cardiac surgery and admitting to the Cardiovascular Intensive Care Unit (CVICU) in the study period were screened for potential inclusion. Demographic information, thyroid hormone and other laboratory measurements and outcome variables were recorded for analysis. Prolonged MV was defined as the duration of MV after cardiac surgery longer than 5 days. Thyroid hormones were assessed for the prognostic significance for prolonged MV.

Results

One thousand eight hundred ninety-six patients who underwent cardiac surgery were screened for potential enrollment. Overall, 118 patients were included and analyzed in this study. Patients fell to the control (n = 64) and the prolonged MV group (n = 54) by complying with the duration of MV after cardiac surgery. The median value of total triiodothyronine (TT3) and free triiodothyronine (FT3) were 1.03 nmol/L and 3.52 pmol/L in the prolonged MV group before cardiac surgery, significantly lower than 1.23 nmol/L (P = 0.005) and 3.87 pmol/L, respectively in control (P = 0.038). Multivariate logistic regression analysis indicated that TT3 before surgery (pre-op TT3) had an excellent prognostic significance for prolonged MV (OR: 0.049,P = 0.012).

Conclusions

This study concluded that decreased triiodothyronine (T3) could be common in cardiac patients with prolonged MV, and it would be further reduced after patients undergo cardiac surgery. Besides, decreased T3 before surgery could act as an effective predictor for prolonged MV after cardiac surgery.
Effects of transcutaneous electrical nerve stimulation on myocardial protection in patients undergoing aortic valve replacement: a randomized clinical trial
Authors: Cho Youn Joung , Jung Dhong-Eun , Nam Karam , Bae Jinyoung , Lee Seohee , Jeon Yunseok
Published: March 2022

Background

Cardiopulmonary bypass-related myocardial ischemia-reperfusion injury is a major contributor to postoperative morbidity. Although transcutaneous electrical nerve stimulation (TENS) has been found to have cardioprotective effects in animal studies and healthy volunteers, its effects on cardiac surgery under cardiopulmonary bypass patients have not been evaluated. We investigated the effects of TENS on myocardial protection in patients undergoing aortic valve replacement surgery using cardiopulmonary bypass.

Methods

Thirty patients were randomized to receive TENS or sham in three different anesthetic states – pre-anesthesia, sevoflurane, or propofol (each n = 5). TENS was applied with a pulse width of 385 μs and a frequency of 10 Hz using two surface electrodes at the upper arm for 30 min. Sham treatment was provided without stimulation. The primary outcome was the difference in myocardial infarct size following ischemia-reperfusion injury in rat hearts perfused with pre- and post-TENS plasma dialysate obtained from the patients using Langendorff perfusion system. The cardioprotective effects of TENS were determined by assessing reduction in infarct size following treatment.

Results

There were no differences in myocardial infarct size between pre- and post-treatment in any group (41.4 ± 4.3% vs. 36.7 ± 5.3%, 39.8 ± 7.3% vs. 27.8 ± 12.0%, and 41.6 ± 2.2% vs. 37.8 ± 7.6%; p = 0.080, 0.152, and 0.353 in the pre-anesthesia, sevoflurane, and propofol groups, respectively).

Conclusions

In our study, TENS did not show a cardioprotective effect in patients undergoing aortic valve replacement surgery.

Trial registration

This study was registered at clinicaltrials.gov (NCT03859115, on March 1, 2019).
Primary tumor resection with or without metastasectomy for left- and right-sided stage IV colorectal cancer: an instrumental variable analysis
Authors: Yao Yi-Chen , Chen Jun-Quan , Yin Ling , Lin Wu-Hao , Peng Jian-Hong , Fan Wen-Hua
Published: March 2022

Background

Whether primary tumor location (PTL) is predictive of survival benefits following primary tumor resection plus metastasectomy (PMTR) and primary tumor resection (PTR) alone in stage IV colorectal cancer patients is not known. We sought to address this issue by employing instrumental variable analysis to evaluate the efficacy of PMTR and PTR with stratification for primary tumor location in stage IV colorectal cancer patients.

Patients and methods

Stage IV colorectal cancer patients diagnosed between January 1, 2005 and December 31, 2015 were identified from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. To account for both measured and unmeasured confounders, the efficacy of PMTR and PTR in the left- and right-sided subgroups was evaluated using instrumental variable analysis, with the health service area as the instrument variable. Overall survival (OS) was the primary outcome of interest.

Results

A total of 50,333 eligible patients were analyzed (left-sided, n = 29,402 and right-sided, n = 20,931). OS was significantly better with PMTR than with other treatments (PTR, metastasectomy only, or no surgery) in patients with left-sided tumors (hazard ratio [HR] = 0.37 [95% CI 0.24–0.58], P < 0.001), but not in patients with right-sided tumors (HR = 0.98 [95% CI 0.65–1.47], P = 0.910; interaction test P < 0.001). OS was comparable in patients treated with PTR and those treated with no surgery in both the left-sided (HR = 1.11 [95% CI 0.68–1.81], P = 0.690) and right-sided (HR = 0.85 [95% CI 0.50–1.43], P = 0.530; interaction test P = 0.466) subgroups.

Conclusions

PMTR appears to only benefit patients with left-sided stage IV colorectal cancer but not those with right-sided tumors. PTR does not improve OS, regardless of primary tumor location. When selecting patients for PMTR, primary tumor location should be considered. Overuse of PTR should be avoided.
Effects and contextual factors of a diet and resistance exercise intervention vary across settings: an overview of three successive ProMuscle interventions
Authors: Dorhout Berber G. , de Groot Lisette C.P.G.M. , van Dongen Ellen J.I. , Doets Esmée L. , Haveman-Nies Annemien
Published: March 2022

Background

Although many effective interventions have been developed, limited interventions have successfully been implemented. An intervention that was translated across settings is ProMuscle: a diet and resistance exercise intervention for older adults. However, varying contexts often lead to varying effects due to contextual factors (characteristics of individuals, organizations, communities or society). The current study aimed to gain insights into effects and contextual factors of ProMuscle in the controlled setting (ProMuscle: PM), real-life setting (ProMuscle in Practice: PiP), and real-life setting of the implementation pilots (ProMuscle Implementation Pilots: IP).

Methods

Data from the intervention arms of PM (N = 31) and PiP (N = 82), and from IP (N = 35) were used. Physical functioning (chair-rise test) and leg strength (1-10 repetition maximum) were measured at baseline and after 12-weeks intervention. Paired t-tests and General Linear Models were used to study changes after 12 weeks and differences between interventions. To explore contextual factors, researchers of PM and physiotherapists and dietitians of PiP and IP were interviewed. Factors were categorized according to the five domains and its underlying constructs of the Consolidated Framework for Implementation Research (CFIR).

Results

Improvements on chair-rise performance were found in PM (-2.0 ± 7.0 s, p = 0.186), PiP (-0.8 ± 2.9 s, p = 0.019) and IP (-3.3 ± 4.2 s, p = 0.001). Similar results were found for leg strength in PM (32.6 ± 24.8 kg, p < 0.001), PiP (17.0 ± 23.2 kg, p < 0.001), and IP (47.8 ± 46.8 kg, p < 0.001). Contextual factors that contribute to explaining the relatively high effects in IP included room for adapting and tailoring the intervention, involvement of experienced professionals, availability of and access to facilities, and participants characteristics.

Conclusions

Effects of the intervention appeared to be strongest in the real-life setting of the implementation pilots. Specific contextual factors contributed to explaining the different findings across settings. Future studies should investigate crucial factors that determine successful implementation of interventions in the real-life setting, to ensure that effective interventions are put into action and reach a broad population.

Trial registration

The ProMuscle intervention was registered in the Trial Registration (clinicaltrials.gov identifier: NCT01110369) on February 12th, 2010. The ProMuscle in Practice intervention was registered in the Netherlands Trial Register (NTR6038) on August 30th, 2016. Trial registration was not needed for the ProMuscle Implementation Pilots as this research did not fall within the remit of the Dutch ‘Medical Research Involving Human Subjects Act’.
Disseminated talaromycosis complicated by recurrent gastrointestinal bleeding and hemorrhagic shock: a case report
Authors: Cui Xiaoya , Su Feifei , Ye Hui , Jiang Yi , Guo Xiuxiu
Published: March 2022

Background

Gastrointestinal involvement is not uncommon in patients with disseminated talaromycosis, but successful management of massive gastrointestinal bleeding and hemorrhagic shock secondary to talaromycosis is rarely reported. Clinical management strategies for these patients have not been well documented.

Case presentation

Here, we reported a case of disseminated talaromycosis with recurrent gastrointestinal bleeding and hemorrhagic shock who was successfully alleviated solely with medical treatment.

Conclusions

Early diagnosis and treatment for Talaromyces marneffei, intravenous fluid resuscitation, hemostatic therapy and blood transfusion are all essential for talaromycosis complicated with gastrointestinal bleeding and hemorrhagic shock. It is also necessary to warn about the possibility of bleeding induced or aggravated by endoscopic biopsy trauma.
Spatial distribution and determinants of bottle feeding among children 0-23 months in Ethiopia: spatial and multi-level analysis based on 2016 EDHS
Authors: Belay Daniel Gashaneh , Getnet Mihret , Akalu Yonas , Diress Mengistie , Gela Yibeltal Yismaw , Getahun Amare Belete , Bitew Desalegn Anmut , Terefe Bewuketu , Belsti Yitayeh
Published: March 2022

Background

Bottle feeding is associated with diarrheal disease morbidity and mortality and risk of pyloric stenosis, especially in developing countries. Even though, World Health Organization (WHO) recommended avoiding bottle feeding among children, still higher magnitude was reported in developing countries. This study aimed to assess the spatial distribution and determinants of bottle feeding among children 0-23 months in Ethiopia.

Methods

This study was conducted based on Ethiopian Demographic and Health Surveys data (EDHS). The data were weighted using sampling weight for probability sampling and non-response to restore the representativeness of the data and get valid statistical estimates. Then a total of 4,275 weighted samples of under two years children were used to investigate the study. The data were cleaned using MS excel and extracted and analyzed using STATA V.16 software. A multilevel binary logistic regression model was fitted. P-value < 0.05 was taken to declare statistical significance. A spatial analysis was done using ArcGIS and SaTScan software.

Results

The prevalence of bottle feeding practice among under two years children in Ethiopia were 13.5% (95%CI: 11.16, 15.29) and ranges from the lowest 5.16% (95% CI: 3.28, 78.73) Amhara region to the highest 55.98% (95% CI: 47.98, 61.46) Addis Ababa region. Women with secondary and above education status [AOR=2.49; 95%CI; 1.66, 3.74], women from richest household [AOR=1.33; 95%CI; 1.01, 1.78], child 12-23 months age [AOR= 1.59; 95%CI; 1.23, 2.05], multiple birth [AOR=4.30; 95%CI; 1.88, 9.84], rural residence [AOR=0.49; 95%CI; 0.16, 0.82] and large central region [AOR= 0.15; 95%CI; 0.08, 0.27] have significantly associated with bottle feeding. Addis Ababa, Central Oromia, Dire Dewa, Somali and Harari regions were the hot spot areas for bottle feeding practice among under two years children.

Conclusion and recommendations

The prevalence of bottle feeding practices in Ethiopia is relatively moderate. Maternal education, wealth index, child age, multiple births, residence and region were significant predictors of bottle feeding. These findings highlight that, the Ministry of Health Ethiopia (MOH), policymakers, and other stakeholders had better give prior attention to preventable factors such as empowering women, enhancing household wealth status to decreasing bottle feeding practice in Ethiopia.
Exploring variation of coverage and access to dental care for adults in 11 European countries: a vignette approach
Authors: Winkelmann Juliane , Gómez Rossi Jesús , Schwendicke Falk , Dimova Antoniya , Atanasova Elka , Habicht Triin , Kasekamp Kaija , Gandré Coralie , Or Zeynep , McAuliffe Úna , Murauskiene Liubove , Kroneman Madelon , de Jong Judith , Kowalska-Bobko Iwona , Badora-Musiał Katarzyna , Motyl Sylwia , Figueiredo Augusto Gonçalo , Pažitný Peter , Kandilaki Daniela , Löffler Lubica , Lundgren Carl , Janlöv Nils , van Ginneken Ewout , Panteli Dimitra
Published: March 2022

Background

Oral health, coupled with rising awareness on the impact that limited dental care coverage has on oral health and general health and well-being, has received increased attention over the past few years. The purpose of the study was to compare the statutory coverage and access to dental care for adult services in 11 European countries using a vignette approach.

Methods

We used three patient vignettes to highlight the differences of the dimensions of coverage and access to dental care (coverage, cost-sharing and accessibility). The three vignettes describe typical care pathways for patients with the most common oral health conditions (caries, periodontal disease, edentulism). The vignettes were completed by health services researchers knowledgeable on dental care, dentists, or teams consisting of a health systems expert working together with dental specialists.

Results

Completed vignettes were received from 11 countries: Bulgaria, Estonia, France, Germany, Republic of Ireland (Ireland), Lithuania, the Netherlands, Poland, Portugal, Slovakia and Sweden. While emergency dental care, tooth extraction and restorative care for acute pain due to carious lesions are covered in most responding countries, root canal treatment, periodontal care and prosthetic restoration often require cost-sharing or are entirely excluded from the benefit basket. Regular dental visits are also limited to one visit per year in many countries. Beyond financial barriers due to out-of-pocket payments, patients may experience very different physical barriers to accessing dental care. The limited availability of contracted dentists (especially in rural areas) and the unequal distribution and lack of specialised dentists are major access barriers to public dental care.

Conclusions

According to the results, statutory coverage of dental care varies across European countries, while access barriers are largely similar. Many dental services require substantial cost-sharing in most countries, leading to high out-of-pocket spending. Socioeconomic status is thus a main determinant for access to dental care, but other factors such as geography, age and comorbidities can also inhibit access and affect outcomes. Moreover, coverage in most oral health systems is targeted at treatment and less at preventative oral health care.
Safeguarding the patient: a grounded theory study of registered nurse anesthetists’ main concerns in the process of extubation in the anesthesia setting
Authors: Rönnberg Linda , Melin-Johansson Christina , Hellzén Ove , Nilsson Ulrica , Häggström Marie
Published: March 2022

Background

The process of extubation is complex as it takes place in the technical and challenging environment of the operating room. The extubation is related to complications of varying severity and a critical moment for the patient, who is in a vulnerable condition when emerging from anesthesia. Registered Nurse Anesthetists (RNAs) in Sweden have specialist training and performs extubations independently or in collaboration with an anesthesiologist.

Aim

To obtain a deeper understanding of Registered Nurse Anesthetists’ main concerns and how they resolve these in the process of extubation when caring for a patient during general anesthesia.

Participants

A total of 17 RNAs, eight male and nine female, were included in the study. Twelve RNAs in the first step of data collection (I); and five RNAs the second step of data collection (II).

Method

A classic grounded theory approach with a qualitative design was used for this study.

Findings

The RNAs’ main concern in the process of extubation were Safeguarding the patient in a highly technological environment, which the solved by Maintaining adaptability. Facilitators as well as challenges affected how the RNAs solved their main concern and represented the categories: ‘Having a back-up plan’, ‘Getting into the right frame of mind’, ‘Evaluating the patient’s reactions’, ‘Using one’s own experience’, ‘Dealing with uncertainty’, ‘Pressure from others’, and ‘Being interrupted’. The theory, Safeguarding the patient in the process of extubation, emerged.

Conclusion

To be able to safeguard the patient in a highly technological environment, the RNAs must oscillate between facilitators and challenges. By maintaining adaptability, the RNAs resolved the difficulties of oscillating, indicating a need for finding a balance between maintaining attentiveness on what is important to keep the patient safe in the process of extubation and all of the disturbances present in the OR.
Psychiatric pharmaceutical care service across Malaysian hospitals: results from a cross-sectional study
Authors: Abousheishaa Aya Ahmed , Sulaiman Ahmad Hatim , Huri Hasniza Zaman , Kamis Siti Fatimah Binti , Hamidi Hafizah , Ang Wei Chern , Zainal Zainol Akbar bin , Shamsuddin Noorasyikin , Guan Ng Chong
Published: March 2022

Background

Psychiatric pharmaceutical care is the provision of pharmaceutical care services to patients with psychiatric related illnesses or disorders. Several studies have demonstrated the positive influence psychiatric pharmaceutical care on patients’ clinical, humanistic and economic outcomes. This study aimed to examine the extent of psychiatric pharmaceutical care practice in a convenience sample of Malaysian government hospitals and the barriers to the provision of these services.

Methods

An anonymous cross-sectional survey of registered pharmacists working at a convenience sample of government hospitals in Malaysia was undertaken from September 2019 to June 2020.

Results

Pharmacists frequently ensured the appropriateness of the dose (55%), dosage form (47%) and dosing schedule (48%) of the dispensed medications. Most pharmacists infrequently worked with patients and healthcare professionals to develop a pharmacotherapeutic regimen and a corresponding monitoring plan (28%). There was no statistically significant difference in the provision of pharmaceutical care services with respect to gender, age, years of practice, and professional board certification. However, the services offered were influenced by the respondent’s education and pharmacy setting. The obstacles perceived by pharmacists included lack of time (89%), shortage of pharmacy staff (87%), the patients’ inability to comprehend medical information (85%), insufficient demand and acceptance by patients (82%), the lack of official policies and standardised practice protocols (78%), inaccessibility to the patients’ medical records (77%) and the lack of structured communication channels between pharmacists and physicians (75%), the pharmacists lack of knowledge/skills and confidence (78%) and insufficient recognition from physicians to the pharmacists’ skills (76%).

Conclusions

This is the first study to explore the extent and barriers of psychiatric pharmaceutical care in Malaysian hospitals; it highlighted the need for mobilising pharmacists to expand these services.
Naturally acquired antibody kinetics against Plasmodium vivax antigens in people from a low malaria transmission region in western Thailand
Authors: Liu Zoe Shih-Jung , Sattabongkot Jetsumon , White Michael , Chotirat Sadudee , Kumpitak Chalermpon , Takashima Eizo , Harbers Matthias , Tham Wai-Hong , Healer Julie , Chitnis Chetan E. , Tsuboi Takafumi , Mueller Ivo , Longley Rhea J.
Published: March 2022

Background

Plasmodium vivax (P. vivax) is the dominant Plasmodium spp. causing the disease malaria in low-transmission regions outside of Africa. These regions often feature high proportions of asymptomatic patients with sub-microscopic parasitaemia and relapses. Naturally acquired antibody responses are induced after Plasmodium infection, providing partial protection against high parasitaemia and clinical episodes. However, previous work has failed to address the presence and maintenance of such antibody responses to P. vivax particularly in low-transmission regions.

Methods

We followed 34 patients in western Thailand after symptomatic P. vivax infections to monitor antibody kinetics over 9 months, during which no recurrent infections occurred. We assessed total IgG, IgG subclass and IgM levels to up to 52 P. vivax proteins every 2–4 weeks using a multiplexed Luminex® assay and identified protein-specific variation in antibody longevity. Mathematical modelling was used to generate the estimated half-life of antibodies, long-, and short-lived antibody-secreting cells.

Results

Generally, an increase in antibody level was observed within 1-week post symptomatic infection, followed by an exponential decay of different rates. We observed mostly IgG1 dominance and IgG3 sub-dominance in this population. IgM responses followed similar kinetic patterns to IgG, with some proteins unexpectedly inducing long-lived IgM responses. We also monitored antibody responses against 27 IgG-immunogenic antigens in 30 asymptomatic individuals from a similar region. Our results demonstrate that most antigens induced robust and long-lived total IgG responses following asymptomatic infections in the absence of (detected) boosting infections.

Conclusions

Our work provides new insights into the development and maintenance of naturally acquired immunity to P. vivax and will guide the potential use of serology to indicate immune status and/or identify populations at risk.
Engineering Saccharomyces cerevisiae for the production and secretion of Affibody molecules
Authors: Gast Veronica , Sandegren Anna , Dunås Finn , Ekblad Siri , Güler Rezan , Thorén Staffan , Tous Mohedano Marta , Molin Mikael , Engqvist Martin K. M. , Siewers Verena
Published: March 2022

Background

Affibody molecules are synthetic peptides with a variety of therapeutic and diagnostic applications. To date, Affibody molecules have mainly been produced by the bacterial production host Escherichia coli. There is an interest in exploring alternative production hosts to identify potential improvements in terms of yield, ease of production and purification advantages. In this study, we evaluated the feasibility of Saccharomyces cerevisiae as a production chassis for this group of proteins.

Results

We examined the production of three different Affibody molecules in S. cerevisiae and found that these Affibody molecules were partially degraded. An albumin-binding domain, which may be attached to the Affibody molecules to increase their half-life, was identified to be a substrate for several S. cerevisiae proteases. We tested the removal of three vacuolar proteases, proteinase A, proteinase B and carboxypeptidase Y. Removal of one of these, proteinase A, resulted in intact secretion of one of the targeted Affibody molecules. Removal of either or both of the two additional proteases, carboxypeptidase Y and proteinase B, resulted in intact secretion of the two remaining Affibody molecules. The produced Affibody molecules were verified to bind their target, human HER3, as potently as the corresponding molecules produced in E. coli in an in vitro surface-plasmon resonance binding assay. Finally, we performed a fed-batch fermentation with one of the engineered protease-deficient S. cerevisiae strains and achieved a protein titer of 530 mg Affibody molecule/L.

Conclusion

This study shows that engineered S. cerevisiae has a great potential as a production host for recombinant Affibody molecules, reaching a high titer, and for proteins where endotoxin removal could be challenging, the use of S. cerevisiae obviates the need for endotoxin removal from protein produced in E. coli.
Rcl1 suppresses tumor progression of hepatocellular carcinoma: a comprehensive analysis of bioinformatics and in vitro experiments
Authors: Jiaze Yu , Sinan Hou , Minjie Yang , Yongjie Zhou , Nan Du , Liangwen Wang , Wen Zhang , Jianjun Luo , Zhiping Yan
Published: March 2022

Background

RNA 3’-terminal phosphate cyclase-like protein (Rcl1) is involved in pre-rRNA processing, but its implication in cancers remains unclear.

Methods

RCL1 expressions in 21 malignancies was examinated through GEPIA website portal. Clinical implication data related to RCL1 level in Hepatocellular Carcinoma (HCC) samples were downloaded through TCGA, ICGC, GEO databases. Survival analysis and gene function enrichment analyses were performed through R software. The correlation between RCL1 expression and tumor immune infiltration was assessed via the TIMER2.0 database. The effects of Rcl1 overexpression or knockdown on cell growth and metastasis was evaluated by CCK8, transwell, and cell cycle assays.

Results

RCL1 expression is commonly down-regulated in HCC. The lower expression of RCL1 is associated with higher tumor stage, higher AFP level, vascular invasion, and poor prognosis. RCL1 expression has a significant correlation with immune cells infiltration in HCC, especially myeloid-derived suppressor cell (MDSC). Moreover, it was further identified that Rcl1 expression was reduced in HCC cell lines and negatively correlated with invasion of HCC cell lines. Immunofluorescence (IF) analysis revealed that the level of Rcl1 expression in the cytoplasm of HCC cells is significantly lower than that in the cytoplasm of L-02 cell. Moreover, both gain- and loss-of-function studies demonstrated that Rcl1 inhibited the growth and metastasis of HCC cells and regulated cell cycle progression in vitro.

Conclusions

Rcl1 may serve as a novel tumor suppressor in HCC, and its biological effect needs further study.
Novel sequential therapy with metformin enhances the effects of cisplatin in testicular germ cell tumours via YAP1 signalling
Authors: He Kancheng , Li Zitaiyu , Ye Kun , Zhou Yihong , Yan Minbo , Qi Hao , Hu Huating , Dai Yingbo , Tang Yuxin
Published: March 2022

Background

Testicular germ cell tumours (TGCTs) are the most commonly diagnosed malignancy in young men. Although cisplatin has been shown to be effective to treat TGCT patients, long-term follow-up has shown that TGCT survivors who accepted cisplatin treatment suffered from a greater number of adverse reactions than patients who underwent orchiectomy alone. As metformin has shown an anticancer effect in various cancers, we investigated whether metformin could enhance the effects of cisplatin to treat TGCTs.

Methods

The anticancer effects of different treatment strategies consisting of metformin and cisplatin in TCam-2 and NTERA-2 cells were assessed in vitro and in vivo. First, we used a colony formation assay, CCK-8 and MTT assays to explore the viability of TGCT cells. Flow cytometry was used to assess the cell cycle and apoptosis of TGCTs. Then, Western blotting was used to detect the protein expression of TGCTs cells after different treatments. In addition, a xenograft model was used to investigate the effects of the different treatments on the proliferation of TGCT cells. Immunohistochemistry assays were performed to analyse the expression of related proteins in the tissues from the xenograft model.

Results

Metformin inhibited the proliferation of TCam-2 and NTERA-2 cells by arresting them in G1 phase, while metformin did not induce apoptosis in TGCT cells. Compared with cisplatin monotherapy, the CCK-8, MTT assay and colony formation assay showed that sequential treatment with metformin and cisplatin produced enhanced anticancer effects. Further study showed that metformin blocked the cells in G1 phase by inducing phosphorylated YAP1 and reducing the expression of cyclin D1, CDK6, CDK4 and RB, which enhanced the chemosensitivity of cisplatin and activated the expression of cleaved caspase 3 in TGCTs.

Conclusions

Our study discovers the important role of YAP1 in TGCTs and reports a new treatment strategy that employs the sequential administration of metformin and cisplatin, which can reduce the required cisplatin dose and enhance the sensitivity of TGCT cells to cisplatin. Therefore, this sequential treatment strategy may facilitate the development of basic and clinical research for anticancer therapies to treat TGCTs.
Resurgent and delayed malaria
Authors: Greenwood Brian , Zongo Issaka , Dicko Alassane , Chandramohan Daniel , Snow Robert W. , Ockenhouse Christian
Published: March 2022

The populations of moderate or highly malaria endemic areas gradually acquire some immunity to malaria as a result of repeated exposure to the infection. When this exposure is reduced as a result of effective malaria control measures, subjects who benefitted from the intervention may consequently be at increased risk of malaria if the intervention is withdrawn, especially if this is done abruptly, and an effective malaria vector remains. There have been many examples of this occurring in the past, a phenomenon often termed ‘rebound malaria’, with the incidence of malaria rebounding to the level present before the intervention was introduced. Because the main clinical burden of malaria in areas with a high level of malaria transmission is in young children, malaria control efforts have, in recent decades, focussed on this group, with substantial success being obtained with interventions such as insecticide treated mosquito nets, chemoprevention and, most recently, malaria vaccines. These are interventions whose administration may not be sustained. This has led to concerns that in these circumstances, the overall burden of malaria in children may not be reduced but just delayed, with the main period of risk being in the period shortly after the intervention is no longer given. Although dependent on the same underlying process as classical ‘resurgent’ malaria, it may be helpful to differentiate the two conditions, describing the later as ‘delayed malaria’. In this paper, some of the evidence that delayed malaria occurs is discussed and potential measures for reducing its impact are suggested.
Curcumin primed ADMSCs derived small extracellular vesicle exert enhanced protective effects on osteoarthritis by inhibiting oxidative stress and chondrocyte apoptosis
Authors: Xu Chen , Zhai Zanjing , Ying Hua , Lu Lin , Zhang Jun , Zeng Yiming
Published: March 2022

Osteoarthritis (OA) is a common joint disease caused by progressive articular cartilage degeneration and destruction. Currently, there are no disease-modifying agents officially approved for OA patients. In this study, curcumin was loaded into adipose tissue-derived mesenchymal stem cells (ADMSCs)-derived small extracellular vesicle (ADMSCs-sEV) to synergistically exert chondro-protective effects in vitro and in vivo. We found curcumin primed ADMSCs derived sEV (sEV-CUR) exhibited an enhanced protective effect compared with free curcumin and ADMSCs-sEV in TBHP-induced chondrocytes. Moreover, our study demonstrated sEV-CUR more effectively down-regulated TBHP-induced oxidative stress and chondrocyte apoptosis in vitro. In OA mice model, our results indicated that sEV-CUR showed an improved cartilage protection, as biweekly intra-articular injection of sEV-CUR more efficaciously alleviated oxidative stress and chondrocyte apoptosis in OA cartilage. Overall, our findings showed sEV-CUR exhibited enhanced chondro-protective effects and holds great potential on the recovery of articular cartilage loss and destruction in OA patients.

Graphical Abstract
Establishment and validation of a prognostic model based on HRR-related lncRNAs in colon adenocarcinoma
Authors: Tang Xingkui , Lin Yukun , He Jialin , Luo Xijun , Liang Junjie , Zhu Xianjun , Li Tao
Published: March 2022

Background

Colon cancer (CRC) is the second leading cause of cancer-related death, and its 5-year survival rate is very low. Homologous recombination repair (HRR) is deficient in most colon cancer. Some long non-coding RNAs (lncRNAs) participate in tumorigenesis of colon cancer through the HRR pathway. We aim to establish a prognostic model based on the HRR-related lncRNAs, expecting to provide a new strategy for precision treatment development in colon cancer.

Methods

Pearson’s correlation was used to identify the HRR-related prognostic lncRNAs in the TCGA-COAD cohort. The TCGA-COAD cohort was randomized into the training set and the testing set. LASSO Cox regression was used to establish the model which was analyzed in the training set and validated in the testing set and the entire TCGA-COAD cohort. Finally, we explored the potential biological function of our model.

Results

A prognostic model was established based on nineteen HRR-related lncRNAs in the training set. COAD patients were scored by the uniform formula and divided into high-risk and low-risk groups based on the median risk score. Patients with high-risk scores indicated poor prognosis in the training set, and the result was confirmed in the testing set and the entire TCGA-COAD cohort (all p < 0.01). Multivariable analysis suggested that our model was an independent factor for overall survival in COAD. The area under the curve (AUC) and C-index indicated that our model had better predictive efficiency than other indicators in the TCGA-COAD cohort. Functional enrichment analysis suggested that our model was associated with the MAPK pathway in COAD. Besides, our model was positively correlated with the HRD scores.

Conclusion

A new prognostic model was established based on nineteen HRR-related lncRNAs which had excellent predictive efficiency on the prognosis of COAD. This prognostic model may provide a new strategy for prognostic prediction of COAD patients.
The role of Staphylococcus aureus enterotoxin B in chronic rhinosinusitis with nasal polyposis
Authors: Chegini Zahra , Didehdar Mojtaba , Khoshbayan Amin , Karami Jafar , Yousefimashouf Milad , shariati Aref
Published: March 2022

CRS with nasal polyps (CRSwNP) is a multifactorial disease, and various etiological factors like bacterial superantigens are known to develop this disease. Recent studies reported that Staphylococcus aureus nasal colonization was detected in 67% of the patients with CRSwNP. Moreover, it was reported that specific IgE against S. aureus enterotoxins are discovered in almost half of the nasal tissue homogenates from nasal polyps. Thus, investigations have highlighted the role of staphylococcal enterotoxins, especially enterotoxin B (SEB), in pathogenesis of CRSwNP. The destruction of mucosal integrity was reported as a main SEB-related pathogenic mechanisms in CRSwNP. SEB activates Toll Like Receptor 2 and triggers the production of pro-inflammatory cytokines; furthermore, it induces reactive oxygen species and endoplasmic reticulum stress-induced inflammation that may cause epithelial cell integrity disruption and enhance their permeability. SEB-induced Type 2/Th2 pathway results in degranulation of eosinophils, cationic proteins production, and localized eosinophilic inflammation. Furthermore, SEB may be involved in the expression of RORC and HIF-1α in Tregs and by maintaining the inflammation in sinonasal mucosa that could have a main role in the pathogenesis of nasal polyposis. Different in vitro findings were confirmed in animal studies; however, in vivo analysis of SEB-induced nasal polyps and CRS remains unfulfilled due to the lack of appropriate animal models. Finally, after elucidating different aspects of SEB pathogenesis in CRSwNP, therapeutic agents have been tested in recent studies with some encouraging results. The purpose of this article is to summarize the most important findings regarding SEB-induced CRS and nasal polyposis.
Magnitude of postpartum hemorrhage and its associated factors in Ethiopia: a systematic review and meta-analysis
Authors: Nigussie Jemberu , Girma Bekahegn , Molla Alemayehu , Tamir Takla , Tilahun Ruth
Published: March 2022

Background

Postpartum hemorrhage or postpartum bleeding (PPH) is often defined as loss of > 500 ml of blood after vaginal delivery or > 1000 ml after cesarean delivery within 24 h. Postpartum hemorrhage is a leading direct cause of maternal morbidity and mortality in Ethiopia. Therefore, the main objective of this systematic review and meta-analysis was to estimate the pooled magnitude of postpartum hemorrhage and the pooled effect size of the associated factors in Ethiopia.

Methods

Primary studies were searched from PubMed/MEDLINE online, Science Direct, Hinari, Cochrane Library, CINAHL, African Journals Online, Google and Google Scholars databases. The searching of the primary studies included for this systematic review and meta-analysis was limited by papers published from 2010 to October 10/2021. The data extraction format was prepared in Microsoft Excel and extracted data was exported to Stata Version 16.0 statistical software for analysis. A random effect meta-analysis model was used. Statistical heterogeneity was evaluated by the I2 test and Egger’s weighted regression test was used to assess publication bias.

Result

A total of 21 studies were included in this meta-analysis. The pooled magnitude of postpartum hemorrhage in Ethiopia was 8.24% [(95% CI 7.07, 9.40]. Older age [OR = 5.038 (95% CI 2.774, 9.151)], prolonged labor [OR = 4.054 (95% CI 1.484, 11.074)], absence of anti-natal care visits (ANC) [OR = 13.84 (95% CI 5.57, 34.346)], grand-multiparty [OR = 6.584 (95% CI 1.902, 22.795)], and history of postpartum hemorrhage [OR = 4.355 (95% CI 2.347, 8.079)] were factors associated with the occurrence of postpartum hemorrhage.

Conclusions

The pooled magnitude of postpartum hemorrhage among post-natal mothers in Ethiopia was moderately high. The finding of this study will strongly help different stakeholder working in maternal and child health to focus on the main contributors’ factors to reduce post-partum hemorrhage among postnatal mothers. Health professionals attending labor and delivery should give more attention to advanced aged mothers, grand-multipara mothers and mothers who had a history of post-partum hemorrhage due to higher risk for postpartum hemorrhage. Encouraging to continue ANC visit and prevent prolonged labor should also be recommended to decrease postpartum hemorrhage.
Clinical and molecular aspects of human pegiviruses in the interaction host and infectious agent
Authors: Samadi Mehdi , Salimi Vahid , Haghshenas Mohammad Reza , Miri Seyed Mohammad , Mohebbi Seyed Reza , Ghaemi Amir
Published: March 2022

Background

Human pegivirus 1 (HPgV-1) is a Positive-sense single-stranded RNA (+ ssRNA) virus, discovered in 1995 as a Flaviviridae member, and the closest human virus linked to HCV. In comparison to HCV, HPgV-1 seems to be lymphotropic and connected to the viral group that infects T and B lymphocytes. HPgV-1 infection is not persuasively correlated to any known human disease; nevertheless, multiple studies have reported a connection between chronic HPgV-1 infection and improved survival in HPgV-1/HIV co-infected patients with a delayed and favorable impact on HIV infection development. While the process has not been thoroughly clarified, different mechanisms for these observations have been proposed. HPgV-1 is categorized into seven genotypes and various subtypes. Infection with HPgV-1 is relatively common globally. It can be transferred parenterally, sexually, and through vertical ways, and thereby its co-infection with HIV and HCV is common. In most cases, the clearance of HPgV-1 from the body can be achieved by developing E2 antibodies after infection.

Main body

In this review, we thoroughly discuss the current knowledge and recent advances in understanding distinct epidemiological, molecular, and clinical aspects of HPgV-1.

Conclusion

Due to the unique characteristics of the HPgV-1, so advanced research on HPgV-1, particularly in light of HIV co-infection and other diseases, should be conducted to explore the essential mechanisms of HIV clearance and other viruses and thereby suggest novel strategies for viral therapy in the future.