bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronicity and COVID-19: Kinship, Illness and the State in Pakistan
Authors: Khan Sanaullah
Published: September 2023

Based on a year-long study involving interviews and surveys among low-income households in Karachi and Lahore, this article describes how participants articulated their experience of the pandemic through ideas of ‘chronicity’ which consisted of poor material conditions, longstanding health problems, and the risks of COVID-19 infections. I consider the bundling of the three elements in relation to the Pakistani state’s imposition of social distancing regulations through its security infrastructure which resulted in reinscribing social differences based on class and religion. Through ethnographic research, I consider how the centrifugal forces at play in the cities at large were negotiated in kinship as members came together during times of illness and emergencies, and conversely, when care to intimate kin was neglected as social distancing practices were taken up selectively in a way that overlapped with deep seated hostilities within families, resulting in further impacting the health of the vulnerable in the absence of adequate health services.
Primary care providers’ perceptions on the integration of community-led advance care planning activities with primary care: a cross-sectional survey
Authors: Carter Rachel Z , Ludwig Monika , Gao Angela , Tan Amy , Barwich Doris , Howard Michelle
Published: September 2023

Background

Advance care planning (ACP) is a process intended to help ensure people receive medical care that is consistent with their values, goals, and preferences during serious and chronic illness. Barriers to implementing ACP in primary care settings exist. Community-led ACP initiatives exist in British Columbia to engage the public directly. These initiatives may help prepare people for conversations with their primary care providers. The objectives of this study were to elicit primary care providers’ perceptions of the utility and desired content of community-led ACP activities and suggestions for integrating community-led ACP activities with primary care.

Methods

We conducted an online cross-sectional survey of primary care providers practicing in British Columbia, Canada in 2021. Both quantitative and qualitative survey questions addressed ACP engagement in practice, the perceived role and desired outcomes of community-led ACP activities, and ways to integrate community-led ACP activities with primary care.

Results

Eighty-one providers responded. Over 80% perceived a moderate or greater potential impact of community-led ACP activities. The most common reasons for not referring a patient to a community-led ACP activity were lack of awareness of the option locally (62.1%) and in general (44.8%). Respondents wanted their patients to reflect on their values, wishes and preferences for care, to have at least thought about their goals of care and to have chosen a substitute decision maker in the community. They indicated a desire for a summary of their patient’s participation and a follow-up discussion with them about their ACP. They suggested ways to integrate referral to programs into existing health care system structures.

Conclusions

Community-led ACP activities were perceived to be useful to engage and prepare patients to continue ACP discussions with clinicians. Efforts should be made to establish and integrate community-based ACP initiatives within existing primary care systems to ensure awareness and uptake.
FIL SSF intraocular lens opacification after pars plana vitrectomy with gas tamponade for traumatic lens luxation and retinal detachment: a case report and literature review
Authors: Iannetta Danilo , Febbraro S. , Valsecchi N. , Moramarco A. , Fontana L.
Published: September 2023

Background

To report a case of sutureless scleral-fixated hydrophilic intraocular lens (FIL SSF IOL, Soleko, Italy) opacification following pars plana vitrectomy surgery using sulfur hexafluoride (SF6) for traumatic lens luxation associated with retinal detachment.

Case presentation

A 77-year-old woman was referred to our emergency department after blunt trauma in her right eye. At the ophthalmic evaluation, visual acuity was hand movement, biomicroscopy showed pseudoexfoliation syndrome and a traumatic lens luxation in the vitreous chamber. The patient underwent pars plana vitrectomy, subluxated cataract explantation, and FIL SSF IOL implant. During surgery, an inferior retinal detachment was encountered, requiring 20% SF6 gas tamponade. No adverse events were encountered. One month postoperatively, visual acuity (BCVA) improved to 0,3 logMAR. At the 3-month follow-up, the patient presented with BCVA of 0,5 logMAR, and biomicroscopy showed a minimal IOL opacification. Six months postoperatively, BCVA decreased to 1.0 logMAR, and diffuse, IOL opacification was noted at slit lamp examination. The patient refused any other surgical intervention for IOL exchange.

Conclusions

Although hydrophilic IOL opacification gas related is known, to the best of our knowledge, this is the first case reported in the literature of FIL SSF IOL opacification after pars plana vitrectomy with gas tamponade for retinal detachment.
Interventional pulmonary procedures and their outcomes in patients with STAT3 hyper IgE syndrome
Authors: Mahdaviani Seyed Alireza , Ghadimi Soodeh , Fallahi Mazdak , Hashemi-Moghaddam Seyedeh Atefeh , Chavoshzadeh Zahra , Puel Anne , Rezaei Nima , Rekabi Mahsa , Daneshmandi Zahra , Sheikhy Kambiz , Kakhki Abolghasem Daneshvar , Saghebi Seyed Reza , Pejhan Saviz , Jamee Mahnaz
Published: September 2023

Background

STAT3 hyperimmunoglobulin E syndrome (STAT3-HIES) also referred to as autosomal dominant HIES (AD-HIES) is an inborn error of immunity characterized by the classic triad of eczema, frequent opportunistic infections, and elevated serum IgE levels. As a consequence of lung sequels due to repeated infections and impaired tissue healing, patients may require interventional pulmonary procedures.

Method

Four patients with dominant-negative STAT3 mutations who had received interventional pulmonary procedures were enrolled. The demographic, clinical, and molecular characteristics were gathered through a medical record search. All reported STAT3-HIES patients in the literature requiring pulmonary procedures as part of their treatment were reviewed.

Result

Recurrent episodes of pneumonia and lung abscess were the most prevalent symptoms. The most common non-immunological features were scoliosis, failure to thrive, and dental problems such as primary teeth retention and disseminated decays. Bronchiectasis, lung abscess, pneumatocele, and cavitary lesion were the most prevalent finding on high-resolution computed tomography at the earliest recording. All patients underwent pulmonary surgery and two of them experienced complications.

Conclusion

Patients with STAT3-HIES have marked pulmonary infection susceptibility which may necessitate thoracic surgeries. Since surgical procedures involve a high risk of complication, surgical options are recommended to be utilized only in cases of drug resistance or emergencies.
Synergistic effects of flavonoids and paclitaxel in cancer treatment: a systematic review
Authors: Asnaashari Solmaz , Amjad Elham , Sokouti Babak
Published: September 2023

Paclitaxel is a natural anticancer compound with minimal toxicity, the capacity to stabilize microtubules, and high efficiency that has remained the standard of treatment alongside platinum-based therapy as a remedy for a variety of different malignancies. In contrast, polyphenols such as flavonoids are also efficient antioxidant and anti-inflammatory and have now been shown to possess potent anticancer properties. Therefore, the synergistic effects of paclitaxel and flavonoids against cancer will be of interest. In this review, we use a Boolean query to comprehensively search the well-known Scopus database for literature research taking the advantage of paclitaxel and flavonoids simultaneously while treating various types of cancer. After retrieving and reviewing the intended investigations based on the input keywords, the anticancer mechanisms of flavonoids and paclitaxel and their synergistic effects on different targets raging from cell lines to animal models are discussed in terms of the corresponding involved signaling transduction. Most studies demonstrated that these signaling pathways will induce apoptotic / pro-apoptotic proteins, which in turn may activate several caspases leading to apoptosis. Finally, it can be concluded that the results of this review may be beneficial in serving as a theoretical foundation and reference for future studies of paclitaxel synthesis, anticancer processes, and clinical applications involving different clinical trials.
The pyrazole derivative of usnic acid inhibits the proliferation of pancreatic cancer cells in vitro and in vivo
Authors: Gimła Mariola , Pyrczak-Felczykowska Agnieszka , Malinowska Marcelina , Hać Aleksandra , Narajczyk Magdalena , Bylińska Irena , Reekie Tristan A. , Herman-Antosiewicz Anna
Published: September 2023

Background

Pancreatic cancer is one of the leading causes of cancer death in Western societies. Its late diagnosis and resistance to chemotherapies result in a high mortality rate; thus, the development of more effective therapies for the treatment of pancreatic cancer is strongly warranted. Usnic acid (UA) is a secondary metabolite of lichens that shows modest antiproliferative activity toward cancer cells. Recently, we reported the synthesis of a UA pyrazole derivative, named 5, which was more active than the parent compound toward cervical cancer cells. Here, its anticancer potential has been evaluated in detail in other cancer cells, particularly pancreatic cancer cells.

Methods

The impact of UA and derivative 5 on cell viability, morphology, cell cycle, and death was assessed using the MTT test, electron microscopy, flow cytometry, and immunoblotting, respectively. The calcium ions level was detected fluorometrically. In vivo, the anticancer activity of 5 was evaluated in a murine xenograft model.

Results

Derivative 5 inhibited the viability of different cancer cells. Noncancerous cells were less sensitive. It induced the release of calcium ions from the endoplasmic reticulum (ER) and ER stress, which was manifested by cell vacuolization. It was accompanied by G0/G1 cell cycle arrest and cell death of pancreatic cancer cells. When applied to nude mice with xenografted pancreatic cancer cells, 5 inhibited tumor growth, with no signs of kidney or liver toxicity.

Conclusions

UA derivative 5 is superior to UA inhibiting the growth and proliferation of pancreatic cancer cells. ER stress exaggeration is a mechanism underlying the activity of derivative 5.
GMP-grade human neural progenitors delivered subretinally protect vision in rat model of retinal degeneration and survive in minipigs
Authors: Lu Bin , Avalos Pablo , Svendsen Soshana , Zhang Changqing , Nocito Laura , Jones Melissa K. , Pieplow Cosmo , Saylor Joshua , Ghiam Sean , Block Amanda , Fernandez Michael , Ljubimov Alexander V. , Small Kent , Liao David , Svendsen Clive N. , Wang Shaomei
Published: September 2023

Background

Stem cell products are increasingly entering early stage clinical trials for treating retinal degeneration. The field is learning from experience about comparability of cells proposed for preclinical and clinical use. Without this, preclinical data supporting translation to a clinical study might not adequately reflect the performance of subsequent clinical-grade cells in patients.

Methods

Research-grade human neural progenitor cells (hNPC) and clinical-grade hNPC (termed CNS10-NPC) were injected into the subretinal space of the Royal College of Surgeons (RCS) rat, a rodent model of retinal degeneration such as retinitis pigmentosa. An investigational new drug (IND)-enabling study with CNS10-NPC was performed in the same rodent model. Finally, surgical methodology for subretinal cell delivery in the clinic was optimized in a large animal model with Yucatan minipigs.

Results

Both research-grade hNPC and clinical-grade hNPC can survive and provide functional and morphological protection in a dose-dependent fashion in RCS rats and the optimal cell dose was defined and used in IND-enabling studies. Grafted CNS10-NPC migrated from the injection site without differentiation into retinal cell phenotypes. Additionally, CNS10-NPC showed long-term survival, safety and efficacy in a good laboratory practice (GLP) toxicity and tumorigenicity study, with no observed cell overgrowth even at the maximum deliverable dose. Finally, using a large animal model with the Yucatan minipig, which has an eye size comparable to the human, we optimized the surgical methodology for subretinal cell delivery in the clinic.

Conclusions

These extensive studies supported an approved IND and the translation of CNS10-NPC to an ongoing Phase 1/2a clinical trial (NCT04284293) for the treatment of retinitis pigmentosa.

Graphical abstract
Urinary peptides provide information about the risk of mortality across a spectrum of diseases and scenarios
Authors: Keller Felix , Beige Joachim , Siwy Justyna , Mebazaa Alexandre , An Dewei , Mischak Harald , Schanstra Joost P. , Mokou Marika , Perco Paul , Staessen Jan A. , Vlahou Antonia , Latosinska Agnieszka
Published: September 2023

Background

There is evidence of pre-established vulnerability in individuals that increases the risk of their progression to severe disease or death, although the mechanisms causing this are still not fully understood. Previous research has demonstrated that a urinary peptide classifier (COV50) predicts disease progression and death from SARS-CoV-2 at an early stage, indicating that the outcome prediction may be partly due to vulnerabilities that are already present. The aim of this study is to examine the ability of COV50 to predict future non-COVID-19-related mortality, and evaluate whether the pre-established vulnerability can be generic and explained on a molecular level by urinary peptides.

Methods

Urinary proteomic data from 9193 patients (1719 patients sampled at intensive care unit (ICU) admission and 7474 patients with other diseases (non-ICU)) were extracted from the Human Urinary Proteome Database. The previously developed COV50 classifier, a urinary proteomics biomarker panel consisting of 50 peptides, was applied to all datasets. The association of COV50 scoring with mortality was evaluated.

Results

In the ICU group, an increase in the COV50 score of one unit resulted in a 20% higher relative risk of death [adjusted HR 1.2 (95% CI 1.17–1.24)]. The same increase in COV50 in non-ICU patients resulted in a higher relative risk of 61% [adjusted HR 1.61 (95% CI 1.47–1.76)], consistent with adjusted meta-analytic HR estimate of 1.55 [95% CI 1.39–1.73]. The most notable and significant changes associated with future fatal events were reductions of specific collagen fragments, most of collagen alpha I (I).

Conclusion

The COV50 classifier is predictive of death in the absence of SARS-CoV-2 infection, suggesting that it detects pre-existing vulnerability. This prediction is mainly based on collagen fragments, possibly reflecting disturbances in the integrity of the extracellular matrix. These data may serve as a basis for proteomics-guided intervention aiming towards manipulating/ improving collagen turnover, thereby reducing the risk of death.
Kynureninase knockdown inhibits cisplatin resistance in vivo and in vitro and impacts the prognosis of cervical adenocarcinoma
Authors: Zhang Jun-wen , Wang Ya-nan , Zhong Mei-ling , Liang Mei-rong
Published: September 2023

Background

Chemotherapy resistance is a leading cause of treatment failure in cases of cervical adenocarcinoma (ADC), and no effective treatment approach has yet been found. We previously identified the differentially expressed kynureninase (KYNU) mRNA in cervical adenocarcinoma cells (HeLa) and cervical adenocarcinoma cisplatin resistance cells (HeLa/DDP) using gene chips. However, the role and potential mechanism of KYNU in the cisplatin resistance of cervical adenocarcinoma remain unclear.

Methods

We verified the expression of KYNU in the cells and tissues of ADC patients and analyzed its correlation with patient prognosis. A stable HeLa/DDP cell line with KYNU mRNA knockdown was constructed. We then used a CCK8 assay to detect cell survival, a transwell assay to evaluate cell migration and proliferation and flow cytometry to measure apoptosis. The effect of KYNU silence on cisplatin sensitivity was evaluated in an orthotopic model of metastatic ADC. Immunohistochemistry was performed to determine the changes in relevant drug resistance-associated protein expression, aiming to explore the underlying mechanism of KYNU-mediated drug resistance.

Results

KYNU is overexpressed in HeLa/DDP cells and tissues and is associated with the poor prognoses of patients with ADC. After KYNU mRNA knockdown, the invasion, migration, and proliferation of HeLa/DDP cells in the cisplatin environment significantly reduced, while the apoptosis rate of HeLa/DDP cells significantly increased. Meanwhile, KYNU knockdown improved the DDP sensitivity of ADC in vivo. Furthermore, silencing KYNU decreased the expressions of CD34 and the drug-resistance related proteins P-gp, MRP1, and GST-π and increased the level of the proapoptotic regulatory protein Bax.

Conclusion

KYNU deficiency enhanced DDP sensitivity by suppressing cell proliferation, migration, and invasion and promoting apoptosis in DDP-resistant ADC cells in vitro. Furthermore, KYNU knockdown improved the drug sensitivity of ADC in vivo. The results showed that KYNU is involved in the chemotherapy resistance of cervical adenocarcinoma.
Predictive value of chemokines (CCL 2) in bronchoalveolar lavage fluid for refractory mycoplasma pneumonia in children
Authors: Zhu Jiangwei , Liu Xue , Zhan Xiaowen , Wang Mengzhu , Zhang Yuling , Na Li , Li Shujun
Published: September 2023

Background

There are relatively few studies investigating C-C motif chemokine ligand 2 (CCL2) level in bronchoalveolar lavage fluid (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP), and the relationship between CCL2 level in BALF and refractory mycoplasma pneumoniae pneumonia (RMPP) is unclear. This study aims to explore the relationship between chemokine CCL2 level in BALF and clinical characteristics and clinical outcome in children with MPP.

Methods

A total of 51 children with confirmed acute MPP and requiring bronchoalveolar lavage in Department of Pediatrics, Huanghe Sanmenxia Hospital and The First Clinical College of Xinxiang Medical University from October 2021 to February 2023 were selected as the study group. And 11 children with bronchial foreign body were selected as the control group. The study group was divided into the non-refractory mycoplasma pneumoniae pneumonia (NRMPP) group and the RMPP group based on the response to treatment. BALF and clinical data of the patients were collected. And CCL2 levels were tested in the patients. Differences in CCL2 level in BALF and clinical characteristics were tested and compared.

Results

The CCL2 level in BALF of the study group was higher than that of the control group, with significant difference (P < 0.05). With ROC curve, the area under the curve (AUC) of CCL2 in BALF predicting RMPP was 0.94, the cut-off value was 0.645 ng/ml, the sensitivity was 85%, and the specificity was 94%, and the diagnostic value was better than that of serum CRP and LDH. Logistic regression analysis was used to build the RMPP prediction model, and CCL2 showed good predictive value.

Conclusion

The level of CCL2 in BALF was high in children with MPP and had a high predictive value for RMPP. CCL2 can be used as one of the biomarkers for predicting RMPP.
Single-plane versus real-time biplane approaches for ultrasound-guided central venous catheterization in critical care patients: a randomized controlled trial
Authors: Li Ying-Ying , Liu Yi-Hao , Yan Lin , Xiao Jing , Li Xin-Yang , Ma Jun , Jia Li-Gang , Chen Rui , Zhang Chao , Yang Zhen , Zhang Ming-Bo , Luo Yu-Kun
Published: September 2023

Background

Critical care patients often require central venous cannulation (CVC). We hypothesized that real-time biplane ultrasound-guided CVC would improve first-puncture success rate and reduce mechanical complications. The purpose of this study was to compare the success rate and safety of single-plane and real-time biplane approaches for ultrasound-guided CVC.

Methods

From October 2022 to March 2023, 256 participants with critical illness requiring CVC were randomized to either the single-plane (n = 128) or biplane (n = 128) ultrasound-guided cannulation groups. The success rate, number of punctures, procedure duration, incidence of catheterization-related complications, and confidence score of operators were documented.

Results

The central vein was successfully cannulated in all 256 participants (163 [64%] man and 93 [36%] women; mean age 69 ± 19 [range 13–104 years]), including 182 and 74 who underwent internal jugular vein cannulation (IJVC) and femoral vein cannulation (FVC), respectively. The incidence of successful puncture on the first attempt was higher in the biplane group than that in the single-plane group (91.6% vs. 74.7%; relative risk (RR), 1.226; 95% confidence interval (CI), 1.069–1.405; P = 0.002 for the IJVC and 90.9% vs. 68.3%; RR, 1.331; 95% CI, 1.053–1.684; P = 0.019 for the FVC). The biplane group was also associated with a higher first-puncture single-pass catheterization success rate (87.4% vs. 69.0% and 90.9% vs. 68.3%), fewer undesired punctures (1[1–1(1–2)] vs. 1[1–2(1–4)] and 1[1–1(1–3)] vs. 1[1–2(1–4)]), shorter cannulation time (205 s [162–283 (66–1,526)] vs. 311 s [243–401 (136–1,223)] and 228 s [193–306 (66–1,669)] vs. 340 s [246–499 (130–944)]), and fewer immediate complications (10.5% vs. 28.7% and 9.1% vs. 34.1%) for both IJVC and FVC (all P < 0.05).

Conclusion

Real-time biplane imaging of ultrasound-guided CVCs offers advantages over the single-plane approach for critically ill patients.

Trial registration: This prospective RCT was registered at Chinese Clinical Trial Registry (ChiCTR2200064843). Registered 19 October 2022.
A monocenter, patient-blinded, randomized, parallel-group, non-inferiority study to compare cochlear implant receiver/stimulator device fixation techniques (COMFIT) with and without drilling in adults eligible for primary cochlear implantation
Authors: Markodimitraki Laura M. , Harkel Timen C. ten , Bennink Edwin , Stegeman Inge , Thomeer Hans G. X. M.
Published: September 2023

Background

During the cochlear implantation procedure, the receiver/stimulator (R/S) part of the implant is fixated to prevent postoperative device migration, which could have an adverse effect on the position of the electrode array in the cochlea. We aim to compare the migration rates of two fixation techniques, the bony recess versus the subperiosteal tight pocket without bony sutures.

Methods and analysis

This single-blind randomized controlled trial will recruit a total of 112 primary cochlear implantation adult patients, eligible for implantation according to the current standard of practice. Randomization will be performed by an electronic data capture system Castor EDC, with participants block randomized to either bony recess or standard subperiosteal tight pocket in a 1:1 ratio, stratified by age. The primary outcome of this study is the R/S device migration rate; secondary outcomes include patient-experienced burden using the validated COMPASS questionnaire, electrode migration rate, electrode impedance values, speech perception scores, correlation between R/S migration, electrode array migration and patient complaints, assessment of complication rates, and validation of an implant position measurement method. Data will be collected at baseline, 1 week, 4 weeks, 8 weeks, 3 months, and 12 months after surgery. All data analyses will be conducted according to the intention-to-treat principle.

Discussion

Cochlear implantation by means of creating a tight subperiosteal pocket without drilling a bony seat is a minimally invasive fixation technique with many advantages. However, the safety of this technique has not yet been proven with certainty. This is the first randomized controlled trial that directly compares the minimally invasive technique with the conventional method of drilling a bony seat.

Trial registration

Netherlands Trial Register NL9698. Registered on 31 August 2021.
Synthesis of novel modified acrylamide copolymers for montmorillonite flocculants in water-based drilling fluid
Authors: Faridi Shirin , Mobinikhaledi Akbar , Moghanian Hassan , Shabanian Meisam
Published: September 2023

A study was conducted to treat the water-based drilling fluid through coagulation-flocculation. Innovative modified acrylamide copolymers were utilized as montmorillonite flocculants to improve drilling performance and reduce environmental contamination. A series of acrylamide copolymers was prepared by in situ free radical polymerization in aqueous medium using ammonium persulfate as a radical initiator. The chemical structure of the prepared copolymers was confirmed by FT-IR (Fourier-Transform Infrared Spectroscopy) and the polydispersity indices of the copolymers determined using gel permeation chromatography. Thermal gravimetric analysis showed that the copolymers have a very high temperature tolerance, i.e. they are stable up to 390 °C. In this paper, acrylamide copolymers were used as coagulant with cationic, anionic groups or both of them simultaneously. Consequently, in order to clarify the relationship between inhibitive properties, sedimentation volume measurement, SEM (scanning electron microscope), XRD (X-ray diffraction) and contact angle were adopted. Some factors including molecular weight and molecular chain affecting the interaction between copolymers and clay particles were analyzed. Anionic sample with the highest molecular weight can reduce the interlayer spacing of the hydrated clay to the minimum. Amphoteric sample exhibits the best performance as a coagulant in comparison with other copolymers.
Paxlovid–tacrolimus drug–drug interaction caused severe diarrhea that induced combined diabetic ketoacidosis and a hyperglycemic hyperosmolar state in a kidney transplant patient: a case report
Authors: Luo Wei , He Yu , Wei Mao Gang , Lu Guang Bing , Yi Qun
Published: September 2023

Background

Transplant recipients are at high risk of coronavirus disease 2019, and a timely supply of antivirals should be prioritized for those patients. Complicated drug‒drug interactions limit the use of Paxlovid (nirmatrelvir/ritonavir) coadministered with tacrolimus. Here, we report a patient with a kidney transplant who received Paxlovid and reduced-dose tacrolimus at the same time and suffered a severe tacrolimus toxicity.

Case presentation

We present a 56-year-old man of Han ethnicity with a kidney transplant who suffered from coronavirus disease 2019 twice. For the first infection, the immunosuppressants were substituted by dexamethasone when the patient used Paxlovid, and everything went well. For the second time, tacrolimus at a reduced dose concomitant with Paxlovid caused severe diarrhea, inducing combined diabetic ketoacidosis and a hyperglycemic hyperosmolar state.

Conclusion

This case challenges the dose-adjustment strategy of managing drug‒drug interactions. We suggest that tacrolimus should be stopped when Paxlovid is applied and that corticosteroids could be a good substitution.
Post-translational modification of CDK1–STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties
Authors: Xu Xiaodong , Ding Yimin , Jin Junbin , Xu Chengjie , Hu Wenyi , Wu Songtao , Ding Guoping , Cheng Rui , Cao Liping , Jia Shengnan
Published: September 2023

Background

Pancreatic cancer stem cells (CSCs) promote pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and chemoresistance. Cyclin-dependent kinase 1 (CDK1) plays an important role in tumor initiation in other tumors, but the function of CDK1 in PDAC remains unclear. Fisetin is a bioactive flavonoid with anti-tumor properties in multiple tumors, while its function in CSCs remains elusive.

Results

In this study, we demonstrated that CDK1 was correlated with prognosis and was highly expressed in pancreatic cancer tissue and gemcitabine-resistant cells. Silencing CDK1 impaired tumor stemness and reduced a subset of CSCs. We found that fisetin blocked the kinase pocket domain of CDK1 and inhibited pancreatic CSC characteristics. Using acetylation proteomics analysis and phosphorylation array assay, we confirmed that fisetin reduced CDK1 expression and increased CDK1 acetylation at lysine 33 (K33), which resulted in the suppression of CDK1 phosphorylation. Silencing CDK1 or STAT3 suppressed tumor stemness properties, while overexpressing CDK1 or STAT3 showed the opposite effect. Mutation or acetylation of CDK1 at K33 weakened STAT3 phosphorylation at Y705, impairing the expression of stem-related genes and pancreatic cancer stemness. In addition, lack of histone deacetylase 3 (HDAC3), which deacetylates CDK1, contributed to weakening STAT3 phosphorylation by regulating the post-translational modification of CDK1, thereby decreasing the stemness of PDAC. Moreover, our results revealed that fisetin enhanced the effect of gemcitabine through eliminating a subpopulation of pancreatic CSCs by inhibiting the CDK1–STAT3 axis in vitro and in vivo.

Conclusion

Our findings highlight the role of post-translational modifications of CDK1–STAT3 signaling in maintaining cancer stemness of PDAC, and indicated that targeting the CDK1–STAT3 axis with inhibitors such as fisetin is a potential therapeutic strategy to diminish drug resistance and eliminate PDAC.
Identifying different patterns of emotion dysregulation in adult ADHD
Authors: Martz Emilie , Weiner Luisa , Weibel Sébastien
Published: September 2023

Background

Emotion dysregulation (ED) is a core intrinsic feature of adult presenting Attention Deficit Hyperactivity Disorder (ADHD). However, the clinical expressions of ED are diverse and several questionnaires have been used to measure ED in adults with ADHD. Thus, to date, the characteristics of ED in adult ADHD remain poorly defined. The objective of this study is to identify the different patterns of ED in adults with ADHD.

Methods

A large sample of 460 newly diagnosed adults with ADHD were recruited. Patients completed a total of 20 self-reported questionnaires. Measures consisted in the several facets of ED, but also other clinical features of adult ADHD such as racing thoughts. A factor analysis with the principal component extraction method was performed to define the symptomatic clusters. A mono-dimensional clustering was then conducted to assess whether participants presented or not with each symptomatic cluster.

Results

The factor analysis yielded a 5 factor-solution, including “emotional instability”, “impulsivity”, “overactivation”, “inattention/disorganization” and “sleep problems”. ED was part of two out of five clusters and concerned 67.52% of our sample. Among those patients, the combined ADHD presentation was the most prevalent. Emotional instability and impulsivity were significantly predicted by childhood maltreatment. The ED and the “sleep problems” factors contributed significantly to the patients’ functional impairment.

Conclusions

ED in ADHD is characterized along emotional instability and emotional impulsivity, and significantly contributes to functional impairment. However, beyond impairing symptoms, adult ADHD may also be characterized by functional strengths such as creativity.
Incidence, functional outcomes and cure rate of hematogenous infection in a 2,498 Total Knee Arthroplasties cohort
Authors: Pérez‐Prieto Daniel , Pardo Albert , Fontanellas Albert , Gómez‐Junyent Joan , Hinarejos Pedro , Monllau Joan‐Carles
Published: September 2023

Purpose

The primary aim of the present study is to report the late acute hematogenous (LAH) prosthetic joint infection (PJI) cure rate following Total knee arthroplasty (TKA) treated by means of debridement, antibiotics, and implant retention (DAIR) in a long‐term follow‐up. The secondary purpose is to report the functional outcomes at that follow‐up and to compare them with a non‐infected group.

Material and Methods

This study cohort consists of 2,498 TKA performed from September 2005 to April 2010 that had a minimum follow‐up of 10 years. The diagnosis of PJI and classification into LAH was done in accordance with the Zimmerli criteria. The primary outcome was the failure rate, defined as death before the end of antibiotic treatment, a further surgical intervention for treatment of infection, life‐long antibiotic suppressive treatment or chronic infection. The Knee Society Score (KSS) was used to evaluate clinical outcomes.

Results

Ten patients were diagnosed with acute hematogenous PJI during the study period (0.4%). All of them were managed with DAIR, which was performed by a knee surgeon and/or PJI surgeon. The failure rate was 0% at the 8.5‐year (SD, 2.4) follow‐up mark. The KSS score was 82.1 vs. 84.1 (p n.s.) at final follow‐up.

Conclusion

Although the literature suggests that TKA DAIR for LAH periprosthetic joint infection is associated with high rates of failure, the results presented here suggest a high cure rate with good functional outcomes.

Level of evidence

Level II, prospective cohort study.
Development of a test method for the dynamic drapability of fabrics using reciprocating motion
Authors: Yun Eunbi , Yun Changsang
Published: September 2023

This study aimed to develop a method for measuring the dynamic drapability of fabrics using a reciprocating motion device that mimics the movement created by shaking a piece of fabric. Five types of fabrics were selected based on their drape coefficients and weights, and the lengths of fabrics were determined based on skirt length (50 cm) and dress length (100 cm). The width and speed of the reciprocating motion were considered as the experimental variables. Results of reciprocating motion-based fabric movement analysis revealed that the number of nodes, the position of the first node, amplitude, total length, and area are significant factors for measuring dynamic drapability. It was found that the longer fabrics had more nodes, enabling measurement of various types of fabrics. Furthermore, it was found that a wider reciprocation width under the same speed and a faster reciprocation speed with the same width favorably demonstrated dynamic drapability, resulting in proportionality between the reciprocating motion and the force transmitted to the fabric. Movement analysis of seven selected conditions and additional samples showed that the optimal condition was a 100-mm reciprocation width and a 150-rpm speed and that the first node’s position is the most significant factor for a dynamic drapability. To verify the proposed measurement method, measuring four pairs of fabrics with similar drape coefficients but different shapes showed that as fabric weight increased, the node moved downward, despite similar drape coefficient values. This confirms that the proposed method can overcome the limitations of the existing drape coefficient.
Hemophagocytic lymphohistiocytosis secondary to unrecognized Bartonella henselae infection: a case report
Authors: Hempel Amanda , Manzoor Fizza , Petrescu Dan
Published: September 2023

Background

Bartonella henselae is a species of intracellular bacteria transmitted to humans through animal bites and scratches contaminated with the feces of arthropod vectors, and are most commonly associated with cat exposure although transmission from other mammals has been reported. Bartonella henselae infection has a spectrum of clinical manifestations and has rarely been reported as cause of hemophagocytic lymphohistiocytosis (HLH) in immunocompromised hosts.

Case presentation

We present a report of Bartonella henselae infection progressing to HLH in an immunocompetent patient. The patient initially presented with regional lymphadenopathy but the diagnosis was not suspected as the patient reported no exposure to cats. On further history, he did report a scratch from a dog prior to development of symptoms. The patient was treated with methylprednisolone, intravenous immunoglobulin and anakinra for the HLH and three months of Doxycycline for Bartonella infection, with complete resolution of symptoms.

Conclusions

Although commonly associated with cat exposure, Bartonella henselae transmission can occur after exposure to other animals and vectors including dogs and clinicians need to maintain an index of suspicion for timely diagnosis. Bartonella henselae is associated with a spectrum of clinical manifestations which can include disseminated infection with severe complications such as hemophagocytic lymphohistiocytosis. Prompt initiation of Bartonella treatment is essential when thought to be the trigger for hemophagocytic lymphohistiocytosis although the optimal treatment regimen is unclear.
Praxeological learning approach in the development of pre-service EFL teachers' TPACK and online information-seeking strategies
Authors: Kulaksız Taibe
Published: September 2023

This study is purposed to implement and test a praxeological learning approach to enhance pre-service EFL teachers’ technological pedagogical content knowledge and online information-seeking skills. This study was conducted based on a convergent parallel mixed design involving thirty-seven sophomore pre-service EFL teachers. Multiple data collection tools were administered at the beginning and end of the course, and data were analyzed aligning with quantitative and qualitative methods complementarily. Active and decisive participation of the pre-service teachers shaped the course design following the sections of independent study, context orientation, and context-based study within the Technological Pedagogical Content Knowledge Framework. Findings showed that pre-service teachers’ technological pedagogical content knowledge and online information-seeking strategies of evaluation, selecting main ideas, and trial & error were significantly improved. Praxeological learning, following the Technological Pedagogical Content Knowledge Framework step-by-step and highlighting context-sensitivity, scaffolded pre-service teachers’ knowledge construction cumulatively and provided them with authentic learning experiences. The praxeological learning approach can support long-term motivation for technology integration knowledge and skills acquisition for pre-service teachers’ future careers.
Estimating the economic value of carbon losses from wildfires using publicly available data sources: Eagle Creek Fire, Oregon 2017
Authors: Sweeney Kristin , Dittrich Ruth , Moffat Spencer , Power Chelsea , Kline Jeffrey D.
Published: September 2023

Background

Wildfires are increasingly frequent in the Western US and impose a number of costs including from the instantaneous release of carbon when vegetation burns. Carbon released into the atmosphere aggravates climate change while carbon stored in vegetation helps to mitigate climate change. The need for climate change mitigation is becoming more and more urgent as achieving the Paris climate agreement target of limiting global warming to 1.5 °C seems ever more challenging. A clear understanding of the role of different carbon sources is required for understanding the degree of progress toward meeting mitigation objectives and assessing the cost and benefits of mitigation policies.

Results

We present an easily replicable approach to calculate the economic cost from carbon released instantaneously from wildfires at state and county level (US). Our approach is straightforward and relies exclusively on publicly available data that can be easily obtained for locations throughout the USA. We also describe how to apply social cost of carbon estimates to the carbon loss estimates to find the economic value of carbon released from wildfires. We demonstrate our approach using a case study of the 2017 Eagle Creek Fire in Oregon. Our estimated value of carbon lost for this medium-sized (19,400 ha) fire is $187.2 million (2020 dollars), which highlights the significant role that wildfires can have in terms of carbon emissions and their associated cost. The emissions from this fire were equivalent to as much as 2.3% of non-fire emissions for the state of Oregon in 2020.

Conclusions

Our results demonstrate an easily replicable method for estimating the economic cost of instantaneous carbon dioxide emissions for individual wildfires. Estimates of the potential economic costs associated with carbon dioxide emissions help to provide a more complete picture of the true economic costs of wildfires, thus facilitating a more complete picture of the potential benefits of wildfire management efforts.
Self-stigma and coping in youth with schizophrenia and bipolar disorder: a comparative study
Authors: Khalaf Ola Osama , Fathy Heba , Ebrahim Hadeer Adel Mostafa , Samie Mai Abdel
Published: September 2023

Background

Self-stigma develops when people with mental disorders start to accept and apply the stigma that the wider public has towards these disorders. People suffering from mental disorders are one of the most groups prone to stigmatization others, making them more likely to experience internalized stigma. Studies done in Europe found that people with schizophrenia had greater internalized stigma than those with mood disorders. Self-stigma has been linked negatively to the individual’s self-esteem, coping, and other outcomes. The aim of this research was to compare young patients with bipolar disorder to those with schizophrenia as regards self-stigma and various coping mechanisms. Additionally, this study sought to evaluate the association between coping mechanisms and self-stigma in young people with schizophrenia and those with bipolar disorder. The ISMI scale and the BRIEF-COPE inventory were used to assess self-stigma and coping strategies respectively.

Results

The mean ISMI total score was significantly higher in the schizophrenia group than in the bipolar disorder group (p < 0.001). The latter group showed a statistically significant higher mean total adaptive score than the schizophrenia group (p = 0.03). A significant positive correlation was found between the total maladaptive score of the BRIEF-COPE inventory and the ISMI scale total score (p < 0.001) in both groups.

Conclusions

Youth with schizophrenia experience more self-stigma than those with bipolar disorder, with the former using more maladaptive coping styles. Self-stigma is strongly linked to maladaptive coping in both schizophrenia and bipolar disorder.
A study on bio-diversity and antiplasmodial activity of rhizosphere soil samples from medicinal plants in Kolli Hills
Authors: Vembaiyan Rajagopalan , Sadasivam Senthilkumar , Singh Vineeta , Gnanadesigan Murugesan
Published: September 2023

Background

Over the previous two decades, Plasmodium falciparum strains have become increasingly resistant to several medications. As a result, there is an urgent need to develop new therapeutic options. Taking this into account, we focused our research on screening microbial extracts from rhizosphere soil samples in specific regions, which increases the likelihood of discovering bacteria capable of producing antiplasmodial activity.

Results

In the current study, we aimed to isolate thirty-two different medicinal plant rhizosphere soil samples collected from Kolli Hills (January–December 2016). Isolation was performed on nutrient and starch casein agar medium by serial dilutions, and distinct colonies were chosen from each dilution. A total of two seventy-five bacterial isolates were isolated from the research plants and kept as pure cultures on nutrient agar. In which, maximum count of fourteen Gram-positive spore forming bacilli strains have been identified and further evaluated for morphological, cultural, and biochemical traits and significantly identified as Bacillus species. Further, promising anti-plasmodial action was demonstrated by B. megaterium bacterial extracts, with IC50 values of 24.65 µg/mL at 24 h and 7.82 µg/mL at 48 h. Bacillus mycoides showed good antiplasmodial activity with (IC50P. falciparum 3D7: 23.52 μg/mL at 24 h and 22.88 μg/mL at 48 h, Bacillus flexus showed IC50 of 18.36 and 6.24 μg/mL and moderate antiplasmodial activity observed in Bacillus tequilensis. Poor antiplasmodial activity was found in Bacillus subtillis, Bacillus macerans, Bacillus pumilus and Bacillus larvey. Interestingly, 16S rRNA sequencing results confirmed that our bacterial species was Bacillus megaterium with 99% similarity observed with the accession number KX495303.1. Additionally, GC–MS analysis revealed effective anti-plasmodial bioactive compounds.

Conclusions

These findings show the potential of B. megaterium from Achyranthes aspera as a antiplasmodial agent. However, more research is needed to fully understand the bioactive compound of these strains and further studies are necessary to explore drug formulation and toxicity levels in the future.
"It's Like You're a Jockey Riding a Horse and You're in a World of Centaurs": Unmasking Autistic College Students' Identity Development
Authors: Nachman Brett Ranon
Published: September 2023

Abstract: As more autistic students enroll in postsecondary education, they embark on a journey that leads them to not only process their identities as college students but also as autistic individuals. This social constructivist grounded theory study elevated autistic college students' perspectives as they made sense of their identities while participating in an autism-specific college support program. The study presents a new conceptual framework: the Nachman Autistic College Student Identity Development Model. This model relays three key stages that influence the sense-making of autistic college students: (a) discovering their disabilities, (b) approaching independence, and (c) determining autistic affiliation. Scholars and practitioners can draw from this model and the study's findings to inform how to account more holistically for autistic college students' iterative identity development.
Traffic Circulation Efficiency of Elliptical Roundabouts
Authors: Fathullah Hardi S. , Majid Hirsh M. , Ahmed Chro H. , Sourkan Sulleyman H. , Ismael Karzan S. , Abdulsamad Balen Z.
Published: September 2023

This paper investigates the impact of geometry of central island of roundabout on operational performance in terms of delay and capacity measures. A roundabout with an elliptical central island having major and minor axes of 63 and 44m respectively was selected as a case study. Using SIDRA Intersection software two simulation models are developed while considering two geometric shapes of central island; one with an elliptical shape and the other with a circular shape. The peak traffic volume of each approach was assigned to both models as a preliminary simulation then twelve scenarios were generated by assigning identical lane volumes starting from a value that gave level of service A and increasing gradually to level of service F. In each scenario 100% of the volume assigned to an approach while the other was assigned with 75% of it and this process was reversed for every run. The results revealed that at high degree of saturation, the elliptical roundabout generally possessed a higher performance especially in term of delay and capacity compared to the circular roundabout. Furthermore, a parametric study was carried out through running eight more simulation scenarios to examine the impacts of heavy vehicle percentage (HV%) on the roundabout operational performance. The (HV %) started from 2% and increased to 12% with alternate approach virtual volume, and  the results showed that performance of the elliptical roundabout was higher than the circular roundabout. However it was more susceptible to increase of HV% in term of control delay and capacity.