bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal patterns of malaria, genital infection, nutritional and iron status in non-pregnant and pregnant adolescents in Burkina Faso: a secondary analysis of trial data
Authors: Roberts Stephen A. , Brabin Loretta , Tinto Halidou , Gies Sabine , Diallo Salou , Brabin Bernard
Published: September 2021

Background

Adolescents are considered at high risk of developing iron deficiency. Studies in children indicate that the prevalence of iron deficiency increased with malaria transmission, suggesting malaria seasonally may drive iron deficiency. This paper examines monthly seasonal infection patterns of malaria, abnormal vaginal flora, chorioamnionitis, antibiotic and antimalarial prescriptions, in relation to changes in iron biomarkers and nutritional indices in adolescents living in a rural area of Burkina Faso, in order to assess the requirement for seasonal infection control and nutrition interventions.

Methods

Data collected between April 2011 and January 2014 were available for an observational seasonal analysis, comprising scheduled visits for 1949 non-pregnant adolescents (≤19 years), (315 of whom subsequently became pregnant), enrolled in a randomised trial of periconceptional iron supplementation. Data from trial arms were combined. Body Iron Stores (BIS) were calculated using an internal regression for ferritin to allow for inflammation. At recruitment 11% had low BIS (< 0 mg/kg). Continuous outcomes were fitted to a mixed-effects linear model with month, age and pregnancy status as fixed effect covariates and woman as a random effect. Dichotomous infection outcomes were fitted with analogous logistic regression models.

Results

Seasonal variation in malaria parasitaemia prevalence ranged between 18 and 70% in non-pregnant adolescents (P < 0.001), peaking at 81% in those who became pregnant. Seasonal variation occurred in antibiotic prescription rates (0.7–1.8 prescriptions/100 weekly visits, P < 0.001) and chorioamnionitis prevalence (range 15–68%, P = 0.026). Mucosal vaginal lactoferrin concentration was lower at the end of the wet season (range 2–22 μg/ml, P < 0.016), when chorioamnionitis was least frequent. BIS fluctuated annually by up to 53.2% per year around the mean BIS (5.1 mg/kg2, range 4.1–6.8 mg/kg), with low BIS (< 0 mg/kg) of 8.7% in the dry and 9.8% in the wet seasons (P = 0.36). Median serum transferrin receptor increased during the wet season (P < 0.001). Higher hepcidin concentration in the wet season corresponded with rising malaria prevalence and use of prescriptions, but with no change in BIS. Mean Body Mass Index and Mid-Upper-Arm-Circumference values peaked mid-dry season (both P < 0.001).

Conclusions

Our analysis supports preventive treatment of malaria among adolescents 15–19 years to decrease their disease burden, especially asymptomatic malaria. As BIS were adequate in most adolescents despite seasonal malaria, a requirement for programmatic iron supplementation was not substantiated.
Clinical characteristics of patients with chronic cough in Guangdong, China: a multicenter descriptive study
Authors: Lai Kefang , Huang Lianrong , Zhao Haijin , Wu Feng , Zhen Guocui , Deng Haiyan , Luo Wei , Peng Wen , Jiang Mei , Yi Fang , Sun Jianxin , Xu Pusheng , Zhou Yuqi , Xu Yinji , Yuan Xiaoling , Zhao Yiju , Chen Meihua , Jiang Yong
Published: September 2021

Background

The clinical characteristics of patients with chronic cough are reported only in single-center survey in China, being significantly different from that in western countries. Here, we performed a multicenter study to describe the clinical characteristics of chronic cough patients.

Methods

A cross-sectional observational survey was conducted in thirteen tertiary hospitals of Guangdong, South China. Relevant data were recorded using a standardized questionnaire and analyzed, including demographics, educational attainment, cough features, and concomitant symptoms.

Results

Of 933 patients in this study, the median age was 40.0 (IQR 31.0–52.0) years with a peaked age of 30–39 years. The proportion of females (487, 52.2 %) was comparable to that of males (446, 47.8 %). Up to 81.9 % of the patients were non-smokers. More than two-thirds of the subjects with chronic cough had a low educational level. The median cough duration was 6.0 (IQR 3.0–24.0) months, and 73.0 % of chronic cough patients presented with dry cough. Laryngeal paresthesia was the most common concomitant symptom (704, 75.5 %), followed by rhinitis/sinusitis-related (350, 37.5 %) and respiratory symptoms (322, 34.5 %). Rhinitis/sinusitis-related symptoms more frequently occurred in patients with productive cough than in those with dry cough (49.0 % vs. 33.0 %, P < 0.001). Moreover, female patients displayed an older age and a higher prevalence of nocturnal cough compared to male patients (both P < 0.05).

Conclusions

Our results show an equal gender, young profile and laryngeal paresthesia in patients with chronic cough, and different clinical features between females and males.
Endobronchial valve positioning for alveolar-pleural fistula following ICU management complicating COVID-19 pneumonia
Authors: Donatelli Pierluigi , Trentacosti Fabiana , Pellegrino Maria Rosaria , Tonelli Roberto , Bruzzi Giulia , Andreani Alessandro , Cappiello Gaia Francesca , Andrisani Dario , Gozzi Filippo , Mussini Cristina , Busani Stefano , Cavaliere Gilda Valentina , Girardis Massimo , Bertellini Elisabetta , Clini Enrico , Marchioni Alessandro
Published: September 2021

Background

The main clinical consequences of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection are pneumonia and respiratory failure even requiring mechanical ventilation. In this context, the lung parenchyma is highly prone to ventilator-related injury, with pneumothorax and persistent air leak as the most serious adverse events. So far, endobronchial valve (EBV) positioning has proved efficacious in treating air leaks with a high success rate.

Case presentation

We report, for the first time, two cases of patients affected by SARS-CoV-2-related pneumonia complicated with bacterial super-infection, experiencing pneumothorax and persistent air leaks after invasive mechanical ventilation. Despite the severity of respiratory failure both patients underwent rigid interventional bronchoscopy and were successfully treated through EBV positioning.

Conclusions

Persistent air leaks may result from lung tissue damage due to a complex interaction between inflammation and ventilator-related injury (VILI), especially in the advanced stages of ARDS. EBV positioning seems to be a feasible and effective minimally invasive therapeutic option for treating this subset of patients.
A predictive model for hip abductor strength and knee extensor strength 12 months after total hip arthroplasty with an interaction term
Authors: Sekita Junya , Takahira Naonobu , Iwamura Genki , Watanabe Hiroyuki , Kusaba Atsushi , Kondo Saiji
Published: September 2021

Background

Identifying populations with poor muscle recovery after total hip arthroplasty (THA) is important for postoperative physical therapy. Preoperative muscle strength is a strong factor that determines postoperative muscle strength. However, this effect may depend on other factors. Thus, predictive models with interaction terms are important for accurately predicting postoperative muscle strength. This study aimed to develop a predictive model for lower muscle strength 12 months after THA which incorporates interaction terms.

Methods

Subjects were female patients with hip osteoarthritis who underwent unilateral THA. Patients with locomotor disorders, neurological disorders, or postoperative complications were excluded. Hip abductor and knee extensor strength were measured, and a generalized linear model approach with preoperative muscle strength, age, body weight, height, disease duration, physical activity, and leg extension as explanatory variables was used to identify factors that determine muscle strength 12 months after THA. Models with interaction terms between preoperative muscle strength and other explanatory variables were also examined.

Results

A total of 82 patients were analyzed. Preoperative muscle strength, age, body weight, physical activity, and disease duration were extracted as factors that significantly and independently determine hip abductor and knee extensor strength. The interaction term between preoperative muscle strength and age was identified as a factor that significantly determines knee extensor strength. Regression coefficients for preoperative knee extensor strength and postoperative muscle strength were significant when age was +1 SD, but not when age was -1 SD.

Conclusions

The predictive model demonstrated that lower muscle strength 12 months after THA is determined by preoperative muscle strength, age, weight, physical activity, disease duration, and preoperative muscle strength, with the effect of preoperative muscle strength on knee extensor strength being dependent on age. When predicting postoperative knee extensor strength using preoperative muscle strength, it is important to consider the effect of age.
Incisional hernia repair by synthetic mesh prosthesis in patients with inflammatory bowel disease: a comparative analysis
Authors: Heise Daniel , Schram Charles , Eickhoff Roman , Bednarsch Jan , Helmedag Marius , Schmitz Sophia M. , Kroh Andreas , Klink Christian Daniel , Neumann Ulf Peter , Lambertz Andreas
Published: September 2021

Background

Patients with inflammatory bowel disease (IBD) have a high-life time risk undergoing abdominal surgery and are prone to develop incisional hernias (IH) in the postoperative course. Therefore, we investigated the role of IBD as perioperative risk factor in open ventral hernia repair (OVHR) as well as the impact of IBD on hernia recurrence during postoperative follow-up.

Methods

The postoperative course of 223 patients (Non-IBD (n = 199) and IBD (n = 34)) who underwent OVHR were compared by means of extensive group comparisons and binary logistic regressions. Hernia recurrence was investigated in the IBD group according to the Kaplan–Meier method and risk factors for recurrence determined by Cox regressions.

Results

General complications (≥ Clavien-Dindo I) occurred in 30.9% (72/233) and major complications (≥ Clavien-Dindo IIIb) in 7.7% (18/233) of the overall cohort with IBD being the single independent risk-factor for major complications (OR = 4.2, p = 0.007). Further, IBD patients displayed a recurrence rate of 26.5% (9/34) after a median follow-up of 36 months. Multivariable analysis revealed higher rates of recurrence in patients with ulcerative colitis (UC, 8/15, HR = 11.7) compared to patients with Crohn’s disease (CD, 1/19, HR = 1.0, p = 0.021).

Conclusion

IBD is a significant risk factor for major postoperative morbidity after OVHR. In addition, individuals with IBD show high rates of hernia recurrence over time with UC patients being more prone to recurrence than patients with CD.
Prosthetic complications of fixed dental prostheses supported by locking-taper implants: a retrospective study with a mean follow-up of 5 years
Authors: Gao Wen mo , Geng Wei , Luo Chen chen
Published: September 2021

Background

Restoration with locking-taper implants is a widely used methodology. However, conical connection systems such as locking-taper implant systems have rarely been examined. This study provides a retrospective investigation of locking-taper fixed restorations, mainly focusing on prosthetic complications.

Methods

Patients undergo treatment with conical connected implants from 2008 to 2010 were examined. Preparation of the implant sites was performed according to the standard procedures for the Bicon system. Bone healing took over 6 months, and the prosthetic procedure was initiated thereafter. Integrated abutment crowns or gold porcelain crowns were used, and the prosthesis type was a single crown or a fixed dental prosthesis. Once the crown was in place, its occlusion was thoroughly checked and adjusted, and then the crown was glazed or finely polished. The Kaplan–Meier method was used to calculate the cumulative complication-free rates for 5 and 10 years. Additionally, a Cox regression model was used to identify the factors that independently influenced the results. Implant survival and marginal bone loss were also investigated.

Results

A total of 392 patients who underwent 541 implants and 434 locking taper implant-based restorations from 2008 to 2010 were examined. The overall 5-year cumulative complication-free rate was 83.34%. The most common prosthetic complication was veneer chipping, with a frequency of 67.53%. According to the Cox regression model, the complication-free rate of integrated abutment crowns was significantly higher than that of gold porcelain crowns, that of molar regions was significantly higher than that of premolar regions, and that of females was significantly higher than that of males. Only three implant failures happened, and the mean marginal bone loss values at 1- year, 5-years and 10- years were 0.25 mm (95% CI ± 0.12), 0.40 mm (95% CI ± 0.03) and 0.51 mm (95% CI ± 0.05), respectively.

Conclusion

Veneer chipping was the most common complication with locking-taper implant-supported fixed restorations. The incidence of complications for IACs is significantly higher than that for GPCs. Age, location, and prosthesis type are not determinants of prosthetic complications. Besides, the long-term clinical effect of locking-taper implant can meet the clinical needs. The bone tissue level around the implant can maintain long-term stability.
Undergraduate audiology students’ perceived competence and confidence in conducting otoscopic examination following video otoscopic training
Authors: Sebothoma Ben , Khoza-Shangase Katijah
Published: September 2021

Background

Emerging research indicates that video otoscopy can be used as a teaching tool to enhance students’ ability to identify outer and middle ear pathologies. However, there is little research on the perceptions of audiology students regarding their competence and confidence following video otoscopic training, and how they view the use of video otoscopy as a teaching tool. Therefore, this study aimed to determine undergraduate (UG) audiology students’ perceived competence and confidence in conducting otoscopy following training by video otoscopic examination.

Methods

A survey methodology with a cross sectional design was employed. An electronic questionnaire was distributed to all third and fourth year (senior) (N = 79) UG audiology students using Survey Monkey. Ethical approval and permission from relevant stakeholders were obtained. Data were analysed using both descriptive and inferential statistics.

Results

60 % of the students felt competent in performing otoscopy, while 63.3 % felt less competent in interpreting otoscopic examination findings. 43.3 % felt they can confidently and competently identify outer ear pathologies. There was no association between the number of video otoscopic examinations performed and perceived competence or/and confidence. There was also no statistically significant relationship between year of study (e.g., third year versus fourth year) and perceived competence or/and confident (p = 0.7131). Almost all (97 %) students felt that video otoscopic training should continue to be part of the clinical training as it helped them enhance their skills in performing otoscopy.

Conclusions

Current findings highlight the need to improve students’ practical training, incorporating pathologic ears into the curriculum. These findings also highlight the importance of supplementing practical training methodologies with changing technological advancements, particularly where tele-audiology opportunities may exist.
Electronic prescription as a driver for digitalization in Finnish pharmacies
Authors: Peltoniemi Teijo , Suomi Reima , Peura Sirpa , Lähteenoja Markus N. Y.
Published: September 2021

Background

Finnish community pharmacies have undergone digitalization during the past decade. The introduction of the electronic prescription has had a significant impact on pharmacy workflows, such as the dispensing process. This inevitably has significant sociotechnical implications. We examine the impact of digitalization on the dispensing process and the sociotechnical orientation of a pharmacy.

Methods

We utilize data collected in customer service situations in Finnish community pharmacies at two points in time: in the traditional workflow, when electronic prescriptions were not in use, and in the new direct dispensing workflow, which is the usual delivery model in the case of electronic prescriptions. We analyze this data in terms of changes in workflow efficiency. We also draw on existing literature to build a conceptual model for digitalization in the pharmacy sector from a sociotechnical standpoint.

Results

In the Finnish environment, the results, based on our study sample, show that with electronic prescriptions and the direct dispensing model, the delivery time for a single medication over the counter was reduced by 13%. The results also indicate that the process has become more predictable, as the variation in terms of the workflow lead time has decreased.

Conclusions

The results indicate that the dispensing process has become more efficient in terms of time and throughput as well as more technically oriented and predictable. From a sociotechnical perspective, the results indicate that the technical subsystem has strengthened, and pharmacies have adapted to the new technology in the dispensing process.
Evolution of biofilm-forming pathogenic bacteria in the presence of nanoparticles and antibiotic: adaptation phenomena and cross-resistance
Authors: Mann Riti , Holmes Amy , McNeilly Oliver , Cavaliere Rosalia , Sotiriou Georgios A. , Rice Scott A. , Gunawan Cindy
Published: September 2021

Background

Treatment of bacterial biofilms are difficult and in many cases, expensive. Bacterial biofilms are naturally more resilient to antimicrobial agents than their free-living planktonic counterparts, rendering the community growth harder to control. The present work described the risks of long-term use of an important alternative antimicrobial, silver nanoparticles (NAg), for the first time, on the dominant mode of bacterial growth.

Results

NAg could inhibit the formation as well as eradicating an already grown biofilm of Pseudomonas aeruginosa, a pathogen notorious for its resilience to antibiotics. The biofilm-forming bacterium however, evolved a reduced sensitivity to the nanoparticle. Evidence suggests that survival is linked to the development of persister cells within the population. A similar adaptation was also seen upon prolonged exposures to ionic silver (Ag+). The persister population resumed normal growth after subsequent passage in the absence of silver, highlighting the potential risks of recurrent infections with long-term NAg (and Ag+) treatments of biofilm growth. The present study further observed a potential silver/antibiotic cross-resistance, whereby NAg (as well as Ag+) could not eradicate an already growing gentamicin-resistant P. aeruginosa biofilm. The phenomena is thought to result from the hindered biofilm penetration of the silver species. In contrast, both silver formulations inhibited biofilm formation of the resistant strain, presenting a promising avenue for the control of biofilm-forming antibiotic-resistant bacteria.

Conclusion

The findings signify the importance to study the nanoparticle adaptation phenomena in the biofilm mode of bacterial growth, which are apparently unique to those already reported with the planktonic growth counterparts. This work sets the foundation for future studies in other globally significant bacterial pathogens when present as biofilms. Scientifically based strategies for management of pathogenic growth is necessary, particularly in this era of increasing antibiotic resistance.

Graphic abstract
Breast myeloid sarcoma presenting as a palpable breast lump after allogeneic stem cell transplantation for acute myelomonocytic leukemia: a rare case report
Authors: Huang Chengmin , Fei Shengqi , Yao Jiang , Chen Panpan , Luo Jiaqing , Wang Yaqi , Li Jie , Wang Weilan
Published: September 2021

Background

Myeloid sarcoma (MS) is a tumor secondary to myeloid leukemia that consists of immature granulocytes with or without mature granulocytes and is a rare extramedullary manifestation of acute myeloid leukemia (AML).

Case presentation

We report a case of a 34-year-old woman diagnosed with AML-M4 who achieved remission after chemotherapy and received allogeneic stem cell transplantation (allo-SCT) for consolidation. Her past medical history showed that she received bilateral breast implants 7 years ago. This patient underwent ultrasound examination of the breast and multiple bilateral breast nodules were revealed that were not considered by clinicians to be concerning. Several months later, the patient’s bilateral nodules rapidly progressed to large palpable masses. Ultrasound-guided biopsy revealed diffuse infiltration of undifferentiated tumor cells and immunohistochemistry (IHC) indicated that the tumor was positive for myeloperoxidase (MPO), cluster of differentiation (CD) 34, CD43, CD68, CD117, and Ki67. The pathological diagnosis was extramedullary recurrence of AML as MS of breast. After the diagnosis, the patient received systemic chemotherapy and drugs containing cytarabine, azacitidine, and methotrexate. However, 1 year after achieving partial remission, the patient died from intracranial invasion of leukemia, brain herniation, and respiratory failure.

Conclusion

It is necessary for the specialist to have a high suspicion index by careful inquiry of the patient’s medical history if a patient presents at the breast clinic with a breast tumor as the chief complaint. Combining information from the patient’s medical history with a tumor biopsy is critical for obtaining the correct diagnosis of the disease.
Vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy for early cervical cancer: a retrospective pilot study
Authors: Wang Xiaojuan , Li Junwei , Hua Keqin , Chen Yisong
Published: September 2021

Background

Minimally invasive surgery for early cervical cancer is debated. We developed this new vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy for early cervical cancer, and we aimed to evaluate the feasibility and safety of this surgical procedure and observe the early oncologic outcomes.

Methods

From January 2019 to August 2020, patients with early cervical cancer who underwent vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy were studied retrospectively. The clinical characteristics, pathologic outcomes, perioperative outcomes, and follow-up details of the patients were recorded.

Results

Forty-eight patients underwent vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy were included, 14 (29.2%) with stage IB1, 13 (27.1%) with stage IB2, 7 (14.6%) with stage IB3, 10 (20.8%) with stage IIA1, and 4 (8.3%) stage with IA2. The mean age at diagnosis was 50.4 (range 28–72) years old. The mean operative time was 237.3 min (range 162–393), and the mean estimated blood loss was 246.5 ml (range 80–800). No intraoperative complications occurred, and there were no patients who were readmitted. Histological types were distributed as follows: squamous cell carcinoma 72.9%, adenocarcinoma 10.4%, and adenosquamous cell carcinoma 16.7%. There were 2 patients (4.2%) with positive nodes, 20 patients (41.7%) with positive lymphovascular space invasion, and 2 patients (4.2%) with positive parametria. Twenty-eight patients (58.3%) received adjuvant therapy after the operation. With a mean follow-up of 17.7 months (range 6–26), there were no recurrent cases, and 11 patients (22.9%) suffered lower limb lymphoedema.

Conclusions

The vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy might be a feasible technique for early cervical cancer, with promising short-term oncological outcomes and safety. A prospective study with more patients and longer follow-up periods should be performed to further evaluate the safety and oncological outcomes.
Pathophysiological role of calcium channels and transporters in the multiple myeloma
Authors: Li Tingting , Chen Junmin , Zeng Zhiyong
Published: September 2021

Multiple myeloma (MM) is a common malignant tumor of plasma cells. Despite several treatment approaches in the past two decades, MM remains an aggressive and incurable disease in dire need of new treatment strategies. Approximately 70–80% of patients with MM have myeloma bone disease (MBD), often accompanied by pathological fractures and hypercalcemia, which seriously affect the prognosis of the patients. Calcium channels and transporters can mediate Ca2+ balance inside and outside of the membrane, indicating that they may be closely related to the prognosis of MM. Therefore, this review focuses on the roles of some critical calcium channels and transporters in MM prognosis, which located in the plasma membrane, endoplasmic reticulum and mitochondria. The goal of this review is to facilitate the identification of new targets for the treatment and prognosis of MM.
Low serum vitamin D concentration is correlated with anemia, microinflammation, and oxidative stress in patients with peritoneal dialysis
Authors: Zhang Chi , Wang Junsheng , Xie Xiaohui , Sun Dong
Published: September 2021

Background

Peritoneal dialysis (PD) is a form of dialysis to replace the function of kidney, that uses the peritoneum as a dialysis membrane to remove metabolites and water retained in the body. Vitamin D deficiency is prevalent in patients treated with PD. This research investigated the correlation between serum 25-hydroxyvitamin D [25(OH)D] concentration and anemia, microinflammation, and oxidative stress in PD patients.

Methods

62 PD patients and 56 healthy volunteers were recruited in this research. Serum concentrations of 25(OH)D and basic parameters of anemia were detected. The correlation between serum 25(OH)D concentration with anemia, oxidative stress, and microinflammatory state were analyzed.

Results

In the PD group, the concentration of 25(OH)D was lower than the healthy control (HC) group (p < 0.001). Hemoglobin, red blood cell count (RBC), and total iron binding capacity (TIBC) in the PD group was significantly lower (all p < 0.001), while high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) concentrations were significantly higher, than the HC group (all p < 0.001). In the PD group, malondialdehyde (MDA) concentration was higher than in the HC group (p < 0.001), while superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were lower (both p < 0.001). Serum 25(OH)D exhibited positive correlation with hemoglobin (r = 0.4509, p = 0.0002), RBC (r = 0.3712, p = 0.0030), TIBC (r = 0.4700, p = 0.0001), SOD (r = 0.4992, p < 0.0001) and GSH-Px (r = 0.4312, p = 0.0005), and negative correlation with hs-CRP (r = − 0.4040, p = 0.0011), TNF-α (r = − 0.4721, p = 0.0001), IL-6 (r = − 0.5378, p < 0.0001) and MDA (r = − 0.3056, p = 0.0157).

Conclusion

In conclusion, reduced serum 25(OH)D concentrations in PD patients contribute to anemia, oxidative stress and microinflammatory state.
Nuclear HER3 expression improves the prognostic stratification of patients with HER1 positive advanced laryngeal squamous cell carcinoma
Authors: Almadori Giovanni , Coli Antonella , De Corso Eugenio , Mele Dario Antonio , Settimi Stefano , Di Cintio Giovanni , Brigato Francesca , Scannone Domenico , Carey Thomas E. , Paludetti Gaetano , Lauriola Libero , Ranelletti Franco Oreste
Published: September 2021

Background

Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear.

Methods

We performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan–Meier and Cox’s proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination.

Results

Immunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified age at diagnosis, tumor site, HER1, HER3 and age at diagnosis, tumor stage, HER1, HER3, as covariates significantly associated with RFS and OS, respectively. Bootstrapping verified the good fitness of these models for predicting survivals and the optimism-corrected C-indices were 0.76 and 0.77 for RFS and OS, respectively.

Conclusions

Nuclear HER3 expression was strongly associated with favourable prognosis and allows to improve the prognostic stratification of patients with HER1 positive advanced LSCC carcinoma.
Combination strategies to maximize the benefits of cancer immunotherapy
Authors: Zhu Shaoming , Zhang Tian , Zheng Lei , Liu Hongtao , Song Wenru , Liu Delong , Li Zihai , Pan Chong-xian
Published: September 2021

Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary and secondary resistance to single agent immunotherapy often results in treatment failure, and only a minority of patients experience long-term benefits. This review article will discuss the relationship between cancer immune response and mechanisms of resistance to immunotherapy. It will also provide a comprehensive review on the latest clinical status of combination therapies (e.g., immunotherapy with chemotherapy, radiation therapy and targeted therapy), and discuss combination therapies approved by the US Food and Drug Administration. It will provide an overview of therapies targeting cytokines and other soluble immunoregulatory factors, ACT, virotherapy, innate immune modifiers and cancer vaccines, as well as combination therapies that exploit alternative immune targets and other therapeutic modalities. Finally, this review will include the stimulating insights from the 2020 China Immuno-Oncology Workshop co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), the China National Medical Product Administration (NMPA) and Tsinghua University School of Medicine.
Chemotherapy-triggered changes in stromal compartment drive tumor invasiveness and progression of breast cancer
Authors: Plava Jana , Burikova Monika , Cihova Marina , Trnkova Lenka , Smolkova Bozena , Babal Pavel , Krivosikova Lucia , Janega Pavol , Rojikova Lucia , Drahosova Slavka , Bohac Martin , Danisovic Lubos , Kucerova Lucia , Miklikova Svetlana
Published: September 2021

Background

Chemotherapy remains a standard treatment option for breast cancer despite its toxic effects to normal tissues. However, the long-lasting effects of chemotherapy on non-malignant cells may influence tumor cell behavior and response to treatment. Here, we have analyzed the effects of doxorubicin (DOX) and paclitaxel (PAC), commonly used chemotherapeutic agents, on the survival and cellular functions of mesenchymal stromal cells (MSC), which comprise an important part of breast tumor microenvironment.

Methods

Chemotherapy-exposed MSC (DOX-MSC, PAC-MSC) were co-cultured with three breast cancer cell (BCC) lines differing in molecular characteristics to study chemotherapy-triggered changes in stromal compartment of the breast tissue and its relevance to tumor progression in vitro and in vivo. Conditioned media from co-cultured cells were used to determine the cytokine content. Mixture of BCC and exposed or unexposed MSC were subcutaneously injected into the immunodeficient SCID/Beige mice to analyze invasion into the surrounding tissue and possible metastases. The same mixtures of cells were applied on the chorioallantoic membrane to study angiogenic potential.

Results

Therapy-educated MSC differed in cytokine production compared to un-exposed MSC and influenced proliferation and secretory phenotype of tumor cells in co-culture. Histochemical tumor xenograft analysis revealed increased invasive potential of tumor cells co-injected with DOX-MSC or PAC-MSC and also the presence of nerve fiber infiltration in tumors. Chemotherapy-exposed MSC have also influenced angiogenic potential in the model of chorioallantoic membrane.

Conclusions

Data presented in this study suggest that neoadjuvant chemotherapy could possibly alter otherwise healthy stroma in breast tissue into a hostile tumor-promoting and metastasis favoring niche. Understanding of the tumor microenvironment and its complex net of signals brings us closer to the ability to recognize the mechanisms that prevent failure of standard therapy and accomplish the curative purpose.
Successful use of extended cardiopulmonary resuscitation followed by extracorporeal oxygenation after venlafaxine-induced takotsubo cardiomyopathy and cardiac arrest: a case report
Authors: Forsberg Sune , Abazi Lis , Forsman Pär
Published: September 2021

Background

Severe venlafaxine intoxication may cause arrhythmias, cardiac failure, and even cardiac arrest.

Case presentation

A 48-year-old caucasian male with an extensive psychiatric history ingested a high dose of venlafaxine causing a serum venlafaxine concentration of 12.6 mg/L 24 hours after ingestion. Seven hours post-ingestion, he experienced tonic–clonic seizures, and 8 hours later, takotsubo cardiomyopathy was recognized followed by cardiac arrest. The patient was resuscitated with prolonged cardiopulmonary resuscitation including ongoing automatic external compressions during helicopter transportation to a tertiary hospital for extracorporeal membrane oxygenation treatment. Despite a cardiopulmonary resuscitation duration of 2 hours, 36 hours of extracorporeal membrane oxygenation, and a total of 30 days of intensive care, the patient made a full recovery.

Conclusion

In cases of intoxication-induced cardiac arrests among otherwise young and healthy patients, prolonged cardiopulmonary resuscitation and extracorporeal circulation can be a life-saving bridge to recovery.
Experiences of families of public safety personnel: a systematic review protocol of qualitative evidence
Authors: Leroux Janette , Richmond Rachel , Fitzpatrick Sara , Kirkland Hannah , Norris Deborah , Mahar Alyson , MacDermid Joy , Dekel Rachel , Cramm Heidi
Published: September 2021

Background

Public safety occupations are well-recognized to be dangerous and stressful. Despite recent attention on post-traumatic stress injuries among public safety personnel, there has been considerably less attention paid to the ongoing ways in which the risks and requirements associated with those occupations shape family life, and how families respond and adapt to those lifestyle dimensions. This systematic review aims to understand how day-to-day family life is affected and shaped when a family member works in a public safety sector, such as fire, police, paramedic, corrections, and emergency communications.

Methods

Qualitative studies that examine the experiences of families or family members of public safety personnel will be included in this review, with no date or language restrictions. An initial search of Embase and CINAHL will be conducted, followed by an analysis of text words contained in the title and abstract, and of the index terms used to describe the articles. Databases to be searched for published studies include MEDLINE, Embase, Web of Sciences, CINAHL, PsycINFO, and Sociological Abstracts. Titles and abstracts will be screened by two independent reviewers. The full texts of selected studies will be assessed in detail, and findings and their illustrations will be extracted and aggregated. Any disagreements between the reviewers that arise at each stage will be resolved through discussion, or by a third reviewer. Further analysis of the synthesized findings will be informed by family systems theory.

Discussion

The ways that occupational risks and requirements shape family life have been better investigated within other high-risk occupation groups, which has led to productive advancements in organizational policies and supports in the respective sectors. An understanding of the experiences which typify family life ongoing within PSP sectors is a critical gap in the development of meaningful family-informed occupational initiatives and supports.

Systematic review registration

Submitted to PROSPERO for systematic review registration: CRD42020208126
Advances in engineering microbial biosynthesis of aromatic compounds and related compounds
Authors: Dickey Roman M. , Forti Amanda M. , Kunjapur Aditya M.
Published: September 2021

Aromatic compounds have broad applications and have been the target of biosynthetic processes for several decades. New biomolecular engineering strategies have been applied to improve production of aromatic compounds in recent years, some of which are expected to set the stage for the next wave of innovations. Here, we will briefly complement existing reviews on microbial production of aromatic compounds by focusing on a few recent trends where considerable work has been performed in the last 5 years. The trends we highlight are pathway modularization and compartmentalization, microbial co-culturing, non-traditional host engineering, aromatic polymer feedstock utilization, engineered ring cleavage, aldehyde stabilization, and biosynthesis of non-standard amino acids. Throughout this review article, we will also touch on unmet opportunities that future research could address.
Clustering subtypes of breast cancer by combining immunohistochemistry profiles and metabolism characteristics measured using FDG PET/CT
Authors: Kwon Hyun Woo , Lee Jeong Hyeon , Pahk Kisoo , Park Kyong Hwa , Kim Sungeun
Published: September 2021

Background

The aim of this study was to investigate the effect of combining immunohistochemical profiles and metabolic information to characterize breast cancer subtypes.

Methods

This retrospective study included 289 breast tumors from 284 patients who underwent preoperative 18 F-fluorodeoxyglucose (FDG) positron emission tomography/ computed tomography (PET/CT). Molecular subtypes of breast cancer were classified as Hormonal, HER2, Dual (a combination of both Hormonal and HER2 features), and triple-negative (TN). Histopathologic findings and immunohistochemical results for Ki-67, EGFR, CK 5/6, and p53 were also analyzed. The maximum standardized uptake value (SUV) measured from FDG PET/CT was used to evaluate tumoral glucose metabolism.

Results

Overall, 182, 24, 47, and 36 tumors were classified as Hormonal, HER2, Dual, and TN subtypes, respectively. Molecular profiles of tumor aggressiveness and the tumor SUV revealed a gradual increase from the Hormonal to the TN type. The tumor SUV was significantly correlated with tumor size, expression levels of p53, Ki-67, and EGFR, and nuclear grade (all p < 0.001). In contrast, the tumor SUV was negatively correlated with the expression of estrogen receptors (r = − 0.234, p < 0.001) and progesterone receptors (r = − 0.220, p < 0.001). Multiple linear regression analysis revealed that histopathologic markers explained tumor glucose metabolism (adjusted R-squared value 0.238, p < 0.001). Tumor metabolism can thus help define breast cancer subtypes with aggressive/adverse prognostic features.

Conclusions

Metabolic activity measured using FDG PET/CT was significantly correlated with the molecular alteration profiles of breast cancer assessed using immunohistochemical analysis. Combining molecular markers and metabolic information may aid in the recognition and understanding of tumor aggressiveness in breast cancer and be helpful as a prognostic marker.
Use of patient specific 3D printed neurovascular phantoms to simulate mechanical thrombectomy
Authors: Sommer Kelsey N. , Bhurwani Mohammad Mahdi Shiraz , Tutino Vincent , Siddiqui Adnan , Davies Jason , Snyder Kenneth , Levy Elad , Mokin Maxim , Ionita Ciprian N.
Published: September 2021

Background

The ability of the patient specific 3D printed neurovascular phantoms to accurately replicate the anatomy and hemodynamics of the chronic neurovascular diseases has been demonstrated by many studies. Acute occurrences, however, may still require further development and investigation and therefore we studied acute ischemic stroke (AIS). The efficacy of endovascular procedures such as mechanical thrombectomy (MT) for the treatment of large vessel occlusion (LVO), can be improved by testing the performance of thrombectomy devices and techniques using patient specific 3D printed neurovascular models.

Methods

3D printed phantoms were connected to a flow loop with physiologically relevant flow conditions, including input flow rate and fluid temperature. A simulated blood clot was introduced into the model and placed in the proximal Middle Cerebral Artery (MCA) region. Clot location, composition, length, and arterial angulation were varied and MTs were simulated using stent retrievers. Device placement relative to the clot and the outcome of the thrombectomy were recorded for each situation. Digital subtraction angiograms (DSA) were captured before and after LVO simulation. Recanalization outcome was evaluated using DSA as either ‘no recanalization’ or ‘recanalization’. Forty-two 3DP neurovascular phantom benchtop experiments were performed.

Results

Clot angulation within the MCA region had the most significant impact on the MT outcome, with a p-value of 0.016. Other factors such as clot location, clot composition, and clot length correlated weakly with the MT outcome.

Conclusions

This project allowed us to gain knowledge of how such characteristics influence thrombectomy success and can be used in making clinical decisions when planning the procedure and selecting specific thrombectomy tools and approaches.
Predicting the establishment of Diaphorina citri and Tamarixia radiata on Citrus x aurantiifolia orchards based on the plant–psyllid–parasitoid interaction on Murraya paniculata
Authors: Chirinos Dorys T. , Cuadros Italo M. , Velez Junior , Castro Rossana , Sornoza Ginger , Kondo Takumasa
Published: September 2021

Background

The insect vector of Huanglongbing, Diaphorina citri Kuwayama, 1908 (Hemiptera: Lividae) was detected in Ecuador in 2013 and its main parasitoid Tamarixia radiata (Waterston, 1922) (Hymenoptera: Eulophidae) was reported for the first time in 2017. In the citrus production region of Manabí province, Ecuador, D. citri and T. radiata were reported for the first time on Murraya paniculata L. in 2016 and 2018, respectively. D. citri was first found infesting Citrus x aurantiifolia (Christm.) Swingle in Manabí province at the end of 2018. The present study was conducted between August 2018 and May 2021 to: (1) monitor D. citri populations on M. paniculata and C. x aurantiifolia and determine the parasitism rates of T. radiata on D. citri nymphs on both host plants, (2) establish the occurrence of T. radiata parasitizing D. citri on C. x aurantiifolia, and (3) calculate a predictive model for estimating the number of parasitized nymphs on a planting lot of M. paniculata and a C. aurantiifolia orchard.

Results

Diaphorina citri populations on M. paniculata decreased from 11 nymphs (2018–2019) to approximately 2 nymphs per flush (2020). This was associated with a natural increase in parasitism rates of T. radiata from 20% (2018) to 96% in 2020. The regression equation (Y = 2.049Ln (x) + 5.88) was able to estimate the number of parasitized D. citri nymphs based on parasitism on M. paniculata (R2: 0.8315). Tamarixia radiata was first detected on C. x aurantiifolia in July 2020. Populations of D. citri reached 55 nymphs per flush (no parasitism) and subsequently decreased to the minimum level of 14 nymphs per flush (parasitism rates of up to 31%). The model allowed estimating the number of parasitized nymphs by T. radiata on M. paniculata and C. x aurantiifolia, with a maximum deviation of approximately 2 nymphs.

Conclusions

Based on the colonization and establishment of the psyllid–parasitoid interaction on M. paniculata, it is estimated that approximately by the end of 2022, populations of D. citri on C. x aurantiifolia would decline due to the highest percentages of parasitism by T. radiata. High parasitism rates may indicate the potential of T. radiata in conservation biological control and integrated pest management programs.
Automated quantification of deep grey matter structures and white matter lesions using magnetic resonance imaging in relapsing remission multiple sclerosis
Authors: Rizkallah Mina , Hefida Mohamed , Khalil Mohamed , Dawoud Rasha Mahmoud
Published: September 2021

Background

Brain volume loss (BVL) is widespread in MS and occurs throughout the disease course at a rate considerably greater than in the general population. In MS, brain volume correlates with and predicts future disability, making BVL a relevant measure of diffuse CNS damage leading to clinical disease progression, as well as serving as a useful outcome in evaluating MS therapies. The aim of our study was to evaluate the role of automated segmentation and quantification of deep grey matter structures and white matter lesions in Relapsing Remitting Multiple Sclerosis patients using MR images and to correlate the volumetric results with different degrees of disability based on expanded disability status scale (EDSS) scores.

Results

All the patients in our study showed relative atrophy of the thalamus and the putamen bilaterally when compared with the normal control group. Statistical analysis was significant for the thalamus and the putamen atrophy (P value < 0.05). On the other hand, statistical analysis was not significant for the caudate and the hippocampus (P value > 0.05); there was a significant positive correlation between the white matter lesions volume and EDSS scores (correlation coefficient of 0.7505). On the other hand, there was a significant negative correlation between the thalamus and putamen volumes, and EDSS scores (correlation coefficients < − 0.9), while the volumes of the caudate and the hippocampus had a very weak and non-significant correlation with the EDSS scores (correlation coefficients > − 0.35).

Conclusions

The automated segmentation and quantification tools have a great role in the assessment of brain structural changes in RRMS patients, and that it became essential to integrate these tools in the daily medical practice for the great value they add to the current evaluation measures.