bluuebunny/crossref_metadata_2025 huggingface dataset:
An Untenable Burden: Exploring Experiences of Secondary School Nurses Who Encounter Young People with Mental Health Problems
Authors: Moyes Anita , McGough Shirley , Wynaden Dianne
Published: March 2022

School nurses have reported stress and worry caring for young people experiencing mental health problems, but why this occurs and how they respond has not been well-explored. In this study researchers generated a substantive theory of the experiences of secondary school nurses who encountered young people with mental health problems using the original method of grounded theory. Thirty-one Western Australian school nurse participants reported that students presented with complex mental and social health needs that were not easily resolved. This was conceptualized as an untenable burden. Participants countered this by engaging in the three-stage process of tactical prioritizing. During an initial period of strategic assimilation into the school and broader community, participants referred students to external service providers. This was frequently inadequate, and participants found themselves grappling with unmet student mental health needs. Participants responded by implementing nursing strategies for optimizing outcomes in the lives of young people, while simultaneously engaging in managing self to support their own well-being.
Applying Insights on Categorisation, Communication, and Dynamic Decision-Making: A Case Study of a ‘Simple’ Maritime Military Decision
Authors: Edmunds Charlotte E. R. , Harris Adam J. L. , Osman Magda
Published: March 2022

A complete understanding of decision-making in military domains requires gathering insights from several fields of study. To make the task tractable, here we consider a specific example of short-term tactical decisions under uncertainty made by the military at sea. Through this lens, we sketch out relevant literature from three psychological tasks each underpinned by decision-making processes: categorisation, communication and choice. From the literature, we note two general cognitive tendencies that emerge across all three stages: the effect of cognitive load and individual differences. Drawing on these tendencies, we recommend strategies, tools and future research that could improve performance in military domains – but, by extension, would also generalise to other high-stakes contexts. In so doing, we show the extent to which domain general properties of high order cognition are sufficient in explaining behaviours in domain specific contexts.
The false positive rates for detecting keratoconus and potential ectatic corneal conditions when evaluating astigmatic eyes with Scheimpflug Technology
Authors: Henriquez Maria A. , Hadid Marta , Moctezuma Cristobal , Izquierdo Luis , Binder Perry S.
Published: March 2022

Purpose

To quantify the false positive rates for keratoconus (KC) and potential ectatic corneal conditions in highly astigmatism eyes when using published parameters/indices obtained from the Pentacam and Galilei units.

Setting

Oftalmosalud Instituto de Ojos, Lima, Peru.

Design

Prospective cohort study.

Methods

67 consecutive eyes with corneal astigmatism > 1.5 D, with a minimum follow ups of 36 months after an uneventful LASIK procedure were included. Indices for KC and other potential ectatic corneal conditions (subclinical KC, forme fruste KC, suspect KC) were obtained using the Pentacam and Galilei Scheimpflug cameras.

Main outcome measures

The false positive rates for KC and potential ectatic corneal conditions were measured. Cut off values provided by previous studies and company-based parameters were used to assess the rate of false positivity.

Results

The range of false positive rates for a KC diagnosis depending on the lowest and highest cutoff values were: index of height decentration (61% - 1%), index of surface variance (76% - 0%), Posterior elevation (55% - 0%), maximum Ambrosio Relational thickness (100% - 13%), Belin Ambrosio enhanced ectasia display total deviation value (100% - 4%), Average pachymetric progression index (69% - 3%), Pachymetry at the thinnest point (58% - 1%), CSI Center Surround Index (100%), Differential sector index (51%).

Conclusion

The false positive rates for KC and ectatic corneal conditions vary dramatically depending on the cut-off values used. Some indexes used for diagnosis of potential ectatic corneal conditions are inaccurate in normal, highly astigmatic eyes.
Safety of collagen cross linking in advanced keratoconus in a patient with scleroderma
Authors: Chandratreya Madhura , Venugopal Anitha , Ghorpade Aditya
Published: March 2022

A 26-year-old female presented to us with complaints of progressive loss of vision in right eye (RE) since past 6 months. Patient was a known case of generalized systemic sclerosis with hypothyroidism for the past 2 years and was under treatment with a rheumatologist Physical features of scleroderma seen in her included diffuse skin tightness, hyper pigmentation of skin of face, abdomen, thighs, legs and arms, with ulcers on fingers. Her best corrected visual acuity was 20/320 in the RE and 20/20 in the left eye (LE). Slit lamp examination showed Fleischer's ring in the RE cornea, and prominent corneal nerves in the LE cornea. Pentacam evaluation revealed advanced keratoconus in RE and Forme Fruste keratoconus in LE. Corneal ectasia in systemic sclerosis is a rare event. Collagen cross linking procedure when undertaken in auto immune disorders may cause adverse reactions. We present a case of systemic sclerosis with advanced keratoconus, who underwent uneventful collagen crosslinking procedure, with stabilization of the cornea post operatively, seen at 6 months follow up. In this case report we emphasize on the factors which need to be taken into consideration when planning for surgical management like collagen cross linking in a collagen vascular disease such as scleroderma.
A Clinical Decision Support System for Increasing Compliance with Protocols in Chemotherapy of Children with Acute Lymphoblastic Leukemia
Authors: Moghaddasi Hamid , Rahimi Rezvan , Kazemi Alireza , Arjmandi Rafsanjani Khadijeh , Bahoush Gholamreza , Rahimi Forough
Published: March 2022

Objective:

In this survey, a protocol-based Chemotherapy Prescription Decision Support System (CPDSS) was designed and evaluated to reduce medication errors in the chemotherapy process of children with ALL.

Methods:

The CPDSS algorithm was extracted by the software development team based on the protocol used by doctors to treat children with ALL. The ASP.Net MVC and SQL Server 2016 programming languages were used to develop the system. A 3-step evaluation (technical, retrospective, and user satisfaction) was performed on CPDSS designed at 2 children’s hospitals in Tehran. The data were analyzed using descriptive statistics. At the technical evaluation step, users provided recommendations included in the system.

Results:

In the retrospective CPDSS evaluation step, 1281 prescribed doses of the drugs related to 30 patients were entered into the system. CPDSS detected 735 cases of protocol deviations and 57 (95%, CI = 1.25-2.55) errors in prescribed chemotherapy for children with ALL. In the user satisfaction evaluation, the users approved two dimensions of the user interface and functionality of the system.

Conclusions:

With the provision of alerts, the CPDSS can help increase compliance with chemotherapy protocols and decrease the chemotherapy prescribing errors that can improve patient safety.
Vitamin B12 (Cobalamin) Deficiency in Overt and Subclinical Primary Hypothyroidism
Authors: Aon Mohamed , Taha Sherif , Mahfouz Khaled , Ibrahim Mohamed M , Aoun Ahmed H
Published: March 2022

Background:

B12 (cobalamin) deficiency has been reported in hypothyroid patients with variable prevalence rates thus routine screening of hypothyroid patients was recommended by some and discouraged by others. We aimed to assess the prevalence of B12 deficiency among hypothyroid patients and to evaluate for pernicious anemia and celiac disease as etiologies.

Methods:

A total 133 patients were included. Thyroid hormones and thyroid peroxidase (TPO) autoantibodies were measured. Serum B12 was measured and if deficient, intrinsic factor antibodies (IFAB) and tissue transglutaminase (tTG) antibodies were evaluated.

Results:

Our study included 45 patients with overt hypothyroidism (OH), 48 patients with subclinical hypothyroidism (SCH), and 40 patients as controls. Mean age was 34.3 years and 82% were females. TPO antibodies were positive in 73.5% of OH and 51.1% of SCH patients. B12 deficiency was detected in 33.3%, 47.9%, and 37.5% of OH, SCH, and controls, respectively with no significant difference ( P = .334). Borderline-to-low B12 level was more prevalent in the OH and the SCH groups compared to controls (68.9%, 85.4%, and 57.5%, respectively; P = .014). Among B12-deficient hypothyroid patients, 7.5% had positive IFAB and 13.3% had positive tTG antibodies. We did not find a significant association of TPO positivity and B12 deficiency (OR, 0.69; 95% CI 0.3-1.57; P = .147).

Conclusion:

We did not find a higher prevalence of B12 deficiency among hypothyroid patients nor an association with TPO positivity. Borderline B12 levels were more prevalent among hypothyroid patients.
Body Mass Index and Diabetes Mellitus May Predict Poorer Overall Survival of Oral Squamous Cell Carcinoma Patients: A Retrospective Cohort From a Tertiary-Care Centre of a Resource-Limited Country
Authors: Adnan Yumna , Ali Syed Muhammad Adnan , Awan Muhammad Sohail , Zahid Nida , Awan Muhammad Ozair , Afzal Kayani Hammad , Farooqui Hasnain Ahmed
Published: March 2022

Introduction:

Oral squamous cell carcinoma (OSCC) is one of the highest-ranking cancers among both genders in Pakistan. Obesity is linked to a much higher risk for developing multiple cancer types. Individuals with Diabetes mellitus (DM) face an increased risk for developing oral cancer. Hence, the objective of this study was to identify the effect of obesity and DM on the prognosis of OSCC patients.

Methods:

This retrospective cohort analysis was conducted on 386 patients diagnosed and treated for OSCC at The Aga Khan University Hospital, Karachi, Pakistan. Patient information was obtained from hospital medical records. Obesity was defined as having a body mass index (BMI) of ⩾25 kg/m2 according to the WHO Asian cut-offs for BMI. Patient BMI was correlated with diabetes status, clinicopathological features and overall survival. Kaplan-Meier survival analysis was performed, along with univariate and multivariate cox regression analysis to test the effect of obesity and diabetes on overall survival.

Results:

In a set of 386 patients, there were 296 males (76.7%) and 90 females (23.3%). The mean BMI was 24.4 (SD ± 5.25) and 42.7% of patients were found to be obese (⩾25 BMI). 64 patients (16.6%) were diabetic. The risk of death was significantly higher in underweight patients ( P = .035) compared with normal weight individuals. Diabetics had a higher mean BMI compared with non-diabetics. However, DM was not a statistically valid predictor of survival.

Conclusion:

Underweight OSCC patients were at a higher risk of death compared with normal weight OSCC patients.
Towards psychedelic apprenticeship: Developing a gentle touch for the mediation and validation of psychedelic-induced insights and revelations
Authors: Timmermann Christopher , Watts Rosalind , Dupuis David
Published: March 2022

A striking feature of psychedelics is their ability to increase attribution of truth and meaningfulness to specific contents and ideas experienced, which may persist long after psychedelic effects have subsided. We propose that processes underlying conferral of meaning and truth in psychedelic experiences may act as a double-edged sword: while these may drive important therapeutic benefits, they also raise important considerations regarding the validation and mediation of knowledge gained during these experiences. Specifically, the ability of psychedelics to induce noetic feelings of revelation may enhance the significance and attribution of reality to specific beliefs, worldviews, and apparent memories which might exacerbate the risk of iatrogenic complications that other psychotherapeutic approaches have historically faced, such as false memory syndrome. These considerations are timely, as the use of psychedelics is becoming increasingly mainstream, in an environment marked by the emergence of strong commercial interest for psychedelic therapy. We elaborate on these ethical challenges via three examples illustrating issues of validation and mediation in therapeutic, neo-shamanic and research contexts involving psychedelic use. Finally, we propose a pragmatic framework to attend to these challenges based on an ethical approach which considers the embeddedness of psychedelic experiences within larger historical and cultural contexts, their intersubjective character and the use of practices which we conceptualise here as forms of psychedelic apprenticeship. This notion of apprenticeship goes beyond current approaches of preparation and integration by stressing the central importance of validation practices based on empathic resonance by an experienced therapist or guide.
In Vivo Visualized Tracking of Tumor-Derived Extracellular Vesicles Using CRISPR-Cas9 System
Authors: Ye Yangyang , Shi Qian , Yang Ting , Xie Fei , Zhang Xiang , Xu Bin , Fang Jingwen , Chen Jiangning , Zhang Yujing , Li Jing
Published: March 2022

Introduction: Tumor extracellular vesicles (EVs) and their relevance to various processes of tumor growth have been vigorously investigated over the past decade. However, obtaining direct evidence of spontaneous EV transfer in vivo remains challenging. In our previous study, a single-guide RNA (sgRNA): Cas9 ribonucleoprotein complex, which can efficiently delete target genes, was delivered into recipient cells using an engineered EV. Aim: Applying this newly discovered exosomal bio-cargo to track the uptake and distribution of tumor EVs. Methods: Tumor cells of interest were engineered to express and release the sgRNA:Cas9 complex, and a reporter cell/system containing STOP-fluorescent protein (FP) elements was also generated. EV-delivered Cas9 proteins from donor cells were programmed by a pair of sgRNAs to completely delete a blockade sequence and, in turn, recuperated the expression of FP in recipient reporter cells. Thus, fluorescently illuminated cells indicate the uptake of EVs. To improve the efficiency and sensitivity of this tracking system in vivo, we optimized the sgRNA design, which could more efficiently trigger the expression of reporter proteins. Results: We demonstrated the EV-mediated crosstalk between tumor cells, and between tumor cells and normal cells in vitro. In vivo, we showed that intravenously administered EVs can be taken up by the liver. Moreover, we showed that EVs derived from melanoma xenografts in vivo preferentially target the brain and liver. This distribution resembles the manifestation of organotrophic metastasis of melanoma. Conclusion: This study provides an alternative tool to study the distribution and uptake of tumor EVs.
Efficacy and mechanism of stellate ganglion block in patients undergoing carotid endarterectomy
Authors: Zhou Chunwang , Li Mengyuan , Zheng Liyan , Chu Yingxin , Zhang Shubo , Gao Xiujiang , Gao Ping
Published: March 2022

Objectives

Carotid endarterectomy (CEA) is an effective technique for carotid artery stenosis and has been widely used. Stellate ganglion block (SGB) has good effect on the treatment of both painful and non-painful diseases. To investigate the efficacy of SGB in terms of cerebral protection in patients undergoing CEA and to analyze its mechanism

Methods

In this retrospective analysis, 120 patients who underwent CEA were enrolled and divided into study group (SG) (60 cases, general anesthesia and SGB) and control group (CG) (60 cases, general anesthesia). The differences in hemodynamic indexes, middle cerebral artery (MCA) hemodynamic indexes, and endocrine-related indexes between the two groups at the baseline, after induction of anesthesia (induction), and skin incision (incision) were compared. The differences in neurological function and pain level between two groups 1 day pre-operatively (pre-op 1), 1 day postoperatively (POD 1), 2 day postoperatively (POD 2), and 7 day postoperatively (POD 7) were also evaluated. Perioperative adverse events and intraoperative anesthetics dosage were compared between two groups;

Results

The systolic blood pressure, diastolic blood pressure, mean pulse pressure difference, and heart rate of SG at incision were lower than those of the CG ( p < 0.05); Vs, Vd, and Vm of MCA were significantly higher in the SG than in CG at induction and incision ( p < 0.05). Cortisol and aldosterone levels were lower and potassium and insulin levels were higher in the SG than in CG at induction and incision ( p < 0.05); At pre-op 1, POD 1, POD 2, and POD 7, the VAS scores of patients in the SG were significantly lower than those in CG at POD 1, POD 2, and POD 7 ( p < 0.05). The patients in SG showed decreased incidence of perioperative adverse events compared with the CG ( p < 0.05); The consumption of anesthetics in the SG was lower than that in CG ( p < 0.05).

Conclusion

SGB in patients undergoing CEA treatment can improve perioperative cerebral blood supply and reduce the consumption of anesthetics and the incidence of perioperative adverse events, which is safe and feasible as a cerebral protection measure. Meanwhile, SGB may also help stabilize patients’ perioperative hemodynamic indexes, but the result still needs to be supported by further large sample data.
Self-assembling peptide gels promote angiogenesis and functional recovery after spinal cord injury in rats
Authors: Hong Jin Young , Kim Su Hee , Seo Yoojin , Jeon Jooik , Davaa Ganchimeg , Kim Soo Hyun , Hyun Jung Keun
Published: March 2022

Spinal cord injury (SCI) leads to disruption of the blood–spinal cord barrier, hemorrhage, and tissue edema, which impair blood circulation and induce ischemia. Angiogenesis after SCI is an important step in the repair of damaged tissues, and the extent of angiogenesis strongly correlates with the neural regeneration. Various biomaterials have been developed to promote angiogenesis signaling pathways, and angiogenic self-assembling peptides are useful for producing diverse supramolecular structures with tunable functionality. RADA16 (Ac-RARADADARARADADA-NH2), which forms nanofiber networks under physiological conditions, is a self-assembling peptide that can provide mechanical support for tissue regeneration and reportedly has diverse roles in wound healing. In this study, we applied an injectable form of RADA16 with or without the neuropeptide substance P to the contused spinal cords of rats and examined angiogenesis within the damaged spinal cord and subsequent functional improvement. Histological and immunohistochemical analyses revealed that the inflammatory cell population in the lesion cavity was decreased, the vessel number and density around the damaged spinal cord were increased, and the levels of neurofilaments within the lesion cavity were increased in SCI rats that received RADA16 and RADA16 with substance P (rats in the RADA16/SP group). Moreover, real-time PCR analysis of damaged spinal cord tissues showed that IL-10 expression was increased and that locomotor function (as assessed by the Basso, Beattie, and Bresnahan (BBB) scale and the horizontal ladder test) was significantly improved in the RADA16/SP group compared to the control group. Our findings indicate that RADA16 modified with substance P effectively stimulates angiogenesis within the damaged spinal cord and is a candidate agent for promoting functional recovery post-SCI.
A rare case of late myelodysplasia cutis associated with essential thrombocythemia: A case report
Authors: Fournier Suzel , Mailhot Sylvain , Bujold Janie
Published: March 2022

Myelodysplasia cutis is a relatively new described entity that is characterized by cutaneous plaques and nodules representing dermal infiltration of myeloid immature non-blastic cells. It can be related to myelodysplastic syndromes or myeloproliferative disorders. It has distinct clinical and histopathological features in comparison with leukemia cutis. We report an unusual case of late myelodysplasia cutis in a male patient with essential thrombocythemia. It is only the second case reported to be related to this myeloproliferative disorder.
Empowering Personal Knowledge Management Among Teachers in Indonesia: A Multi-Faceted Approach using SEM
Authors: Sudibjo Niko , Aulia Siti , Harsanti HG Retno
Published: March 2022

Previous studies reveal a gap in literature relating the contribution of personal knowledge management (PKM) at the individual level within organization. In addition, the mediating role of organizational learning in the relationship between transformational leadership on personal knowledge management is less studied. Therefore, this study aims to address the gap by investigating the combined effects of transformational leadership, information and communications technology (ICT) literacy, and organizational learning toward teachers’ PKM in the context of school in Indonesia. It is also aimed to explore the role of organizational learning as the mediating variable. We collected questionnaire data from 80 teachers at an international school in Jakarta, Indonesia and used partial least squares structural equation modeling to examine the data. Our findings showed that ICT literacy, transformational leadership, and organizational learning culture positively affect PKM. ICT literacy found to have the biggest impact on the PKM of the teachers. In addition, organizational learning found to mediate the effect of transformational leadership on PKM, even though the increase is not high. These findings provide managerial implications for the school management to improve their ICT literacy by building ICT literacy ecosystem in the school to improve teachers’ PKM.
Upwards Workplace Bullying: A Literature Review
Authors: Busby Lorraine , Patrick Linda , Gaudine Alice
Published: March 2022

There is a large body of international literature on most aspects of workplace bullying, yet there are only a few research articles dealing with bullying of bosses, managers, and leaders by their subordinates and staff members. Over time the term “upwards bullying” has been accepted as the generic term to describe this phenomenon but using these search terms does not provide a comprehensive indication of relevant publications. This literature review identifies and collates English language research on upwards bullying to document its research status, its lack of visibility in the workplace, and to connect upwards bullying with related research on aggression against supervisors and managers. Included is research that specifically labels the phenomena as upwards or upward bullying, along with related terms of subordinate-initiated bullying, supervisor-targeted bullying, bottom-up bullying, bullying the manager, and bullying the boss. Nonacademic publications are not included, nor is research on related workplace misbehavior such as cyberbullying, legal action resulting from upwards bullying or whistle blowers, and extortion or blackmail. Areas for further exploration in the field are identified with indicators of how this type of workplace bullying differs from lateral and downward bullying. Coverage up to the year 2020 is provided with the expectation that the trend of working from home driven by safety considerations during the COVID-19 epidemic could change employee responses and reactions to their workplace leaders and management.
The Impact of Reading Strategy Instruction on Reading Comprehension, Strategy Use, Motivation, and Self-Efficacy in Chinese University EFL Students
Authors: Li Hong , Gan Zhengdong , Leung Shing On , An Zhujun
Published: March 2022

This study investigated the effect of explicit reading strategy instruction on reading comprehension, reading strategy use, reading motivation, and reading self-efficacy in Chinese university EFL learners. A total of 117 first-year university students were randomly assigned to either the experimental group or the control group. Students in the experimental group received a 16-week reading strategy training embedded into their English reading classes. The data were collected through five major instruments: a reading comprehension test, a reading strategy questionnaire, a reading motivation questionnaire, a reading self-efficacy questionnaire, and a semi-structured interview. Independent-samples t-test results showed that there was a significant difference in reading comprehension between the experimental group and the control group after the reading strategy instruction, suggesting that students who received reading strategy instruction made significant improvement in their reading comprehension. ANCOVA analysis of pre- and post-questionnaires results showed that there were no significant changes in reading strategy use, reading motivation, and reading self-efficacy at the end of the strategy instruction. Furthermore, interview data, showed that experimental group students held very positive attitudes toward the reading strategy training. Interview results further suggested that lack of significant changes in strategy use, motivation, and self-efficacy at the end of strategy training could be explained by a dynamic interplay of individual and contextual factors.
A low-shrinkage, hydrophobic, degradation-resistant, antimicrobial dental composite using a fluorinated acrylate and an oxirane
Authors: Bergeron Clara , Ballard Cori , Li Yiming , Zhang Wu , Zhong Zhe , Whang Kyumin
Published: March 2022

Objective:

To develop a low shrinkage, hydrophobic, degradation-resistant, antimicrobial dental composite using a fluorinated acrylate, and a difunctional oxirane.

Methods:

The effects of a fluorinated acrylate (2-(perfluorooctyl)ethyl acrylate; PFOEA), a difunctional oxirane (EPALLOY™ 5001; EP5001), and a three-component initiator system (camphorquinone/ethyl 4-dimethylaminobenzoate/4-Isopropyl-4′-methyldiphenyl iodonium Tetrakis (pentafluorophenyl) borate; CQ/EDMAB/Borate) on bisphenol A glycidyl dimethacrylate: triethylene glycol dimethacrylate (BisGMA:TEGDMA) composite surface hardness, degree of monomer-to-polymer conversion, hydrophobicity, translucency, mechanical properties, polymerization shrinkage and shrinkage stress, degradation, water imbibition, and antimicrobial properties were determined.

Results:

Overall the experimental composites had comparable mechanical properties and lower volumetric polymerization shrinkage and shrinkage stress as compared to BisGMA:TEGDMA controls. Addition of PFOEA increased composite hydrophobicity, but it decreased degree of cure, ultimate transverse strength, and translucency. It also decreased polymerization shrinkage and shrinkage stress. The use of the CQ/EDMAB/Borate initiator system was beneficial for the cure and mechanical properties of the 30% w/w PFOEA group. However, it decreased the hydrophobicity and translucency of those composites. The addition of EP5001, at the low concentration used in this work, did not contribute to reduced polymerization volumetric shrinkage or antimicrobial properties, but it did reduce shrinkage stress.

Conclusions:

A mechanically viable hydrophobic composite system with reduced polymerization shrinkage and shrinkage stress has been developed by adding PFOEA and EP5001. However, the addition of EP5001 did not render the composite antimicrobial due to the low concentration used. Further research is needed to determine the lowest concentration at which EP5001 provides antimicrobial activity. The composites developed here have the potential to improve longevity of traditional BisGMA:TEGDMA composite systems.
Endoscopic Treatment of Black Esophagus With Fully Covered Metallic Stent
Authors: Al Bayati Ihsan , Badhiwala Vismay , Al Obaidi Sarah , Didia Claudia , Zuckerman Marc J. , Elhanafi Sherif
Published: March 2022

Acute esophageal necrosis (AEN) is a condition characterized by black appearance and inflammation of the esophagus. Our patient developed AEN presenting in the setting of alcohol intoxication and extensive inferior vena cava thrombosis. Esophagogastroduodenoscopy showed blood and black discoloration of the middle and lower esophagus with oozing. To control bleeding, a self-expandable fully covered metallic esophageal stent was placed. Multiple studies and reviews agree that the initial management for AEN is supportive care, resuscitation, and proton pump inhibitors to protect the esophageal mucosa from injury from acid reflux. Our case highlights the benefits of esophageal stent placement to manage AEN with active bleeding.
Another Sherlock Holmes Mystery: Abdominal Pain Explained by Median Arcuate Ligament Syndrome
Authors: Ortega Andrew J. , Memon Hadiqa , Trivedi Bhavi , Davis Brian , McCallum Richard
Published: March 2022

Median arcuate ligament syndrome (MALS), also known as celiac artery compression syndrome, is a rare gastrointestinal condition with an estimated incidence of 2 per 100 000 population. Predominantly in female patients, this syndrome is characterized by the compression of the celiac artery at its origin from the aorta by the median arcuate ligament, which at the same time is entrapping the celiac plexus, causing upper abdominal pain, notably postprandial pain, as well as nausea, vomiting, food aversion, and weight loss. We present a case of abdominal pain secondary to MALS that was appropriately diagnosed after requiring narcotic medication, which responded to surgical therapy.
Left Internal Mammary Artery-to-Pulmonary Vein Fistula: A Rare Cause of Unstable Angina
Authors: Ezeh Ebubechukwu , Akhigbe Esiemoghie , Amro Mohammad , Hamilton Mackenzie , Olubowale Olusola , Studeny Mark , Mader Jason
Published: March 2022

The incidence of acquired left internal mammary artery-to-pulmonary vein fistulas has been increasing in the last few decades. This has been attributed to the increase in coronary artery bypass surgery (CABG). The most commonly reported symptoms are angina and dyspnea. The timing of the presentation varies widely from a few months to several years after CABG. Medical management is the treatment of choice and usually controls the symptoms in most patients. Percutaneous intervention is, however, indicated when medical therapy fails. In this case report, a 72-year-old man with a history of CABG presented with progressively worsening chest pain and dyspnea. Troponin was negative and the electrocardiogram showed no acute ischemic changes. He was found to have left internal mammary artery-to-pulmonary vein fistula on coronary angiogram. His symptoms improved upon intensifications of his guideline-directed therapy for coronary artery disease. This represents an unusual cause of unstable angina.
Response-adapted anti-PD-1–based salvage therapy for Hodgkin lymphoma with nivolumab alone or in combination with ICE
Authors: Mei Matthew G. , Lee Hun Ju , Palmer Joycelynne M. , Chen Robert , Tsai Ni-Chun , Chen Lu , McBride Kathryn , Smith D. Lynne , Melgar Ivana , Song Joo Y. , Bonjoc Kimberley-Jane , Armenian Saro , Nwangwu Mary , Lee Peter P. , Zain Jasmine , Nikolaenko Liana , Popplewell Leslie , Nademanee Auayporn , Chaudhry Ammar , Rosen Steven , Kwak Larry , Forman Stephen J. , Herrera Alex F.
Published: March 2022

This phase 2 trial evaluated PET-adapted nivolumab alone or in combination with ifosfamide, carboplatin, and etoposide (NICE) as first salvage therapy and bridge to autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory (RR) classical Hodgkin lymphoma (cHL). Patients with RR cHL received 240 mg nivolumab every 2 weeks for up to 6 cycles (C). Patients in complete response (CR) after C6 proceeded to AHCT, whereas patients with progressive disease at any point or not in CR after C6 received NICE for 2 cycles. The primary endpoint was CR rate per the 2014 Lugano classification at completion of protocol therapy. Forty-three patients were evaluable for toxicity; 42 were evaluable for response. Thirty-four patients received nivolumab alone, and 9 patients received nivolumab+NICE. No unexpected toxicities were observed after nivolumab or NICE. After nivolumab, the overall response rate (ORR) was 81%, and the CR rate was 71%. Among 9 patients who received NICE, all responded, with 8 (89%) achieving CR. At the end of protocol therapy, the ORR and CR rates were 93% and 91%. Thirty-three patients were bridged directly to AHCT, including 26 after Nivo alone. The 2-year progression-free survival (PFS) and overall survival in all treated patients (n = 43) were 72% and 95%, respectively. Among 33 patients who bridged directly to AHCT, the 2-year PFS was 94% (95% CI: 78-98). PET-adapted sequential salvage therapy with nivolumab/nivolumab+NICE was well tolerated and effective, resulting in a high CR rate and bridging most patients to AHCT without chemotherapy. This trial was registered at www.clinicaltrials.gov #NCT03016871.
Bite-size introduction to canine hematologic malignancies
Authors: Atherton Matthew J. , Mason Nicola J.
Published: March 2022

Hematologic malignancies are frequently diagnosed in dogs and result in a spectrum of clinical signs associated with specific disease types. The most frequently encountered hematologic tumors in dogs include lymphoma, lymphoid and myeloid leukemias, and mast cell, plasma cell, and histiocytic neoplasias. Coupled with the heterogeneous presentations of the different categories and subtypes of canine hematologic malignancies, outcomes for these tumors are also variable. Considering this, appropriate treatment options range from active surveillance to curative intent approaches harnessing surgical, chemotherapeutic, and radiation-based modalities. The underlying pathology of many of these diseases bears remarkable resemblance to that of the corresponding diagnosis made in human patients. We introduce some of the pathogenic drivers of canine hematologic cancers alongside their clinical presentations. An overview of standard-of-care therapies for each of these diseases is also provided. As comparative oncology gains recognition as a valuable setting in which to investigate the pathogenesis of neoplasia and provide powerful, clinically relevant, immunocompetent models for the evaluation of novel therapies, the number of clinicians and scientists participating in cancer research involving dogs is expected to increase. This review aims at providing an introductory overview of canine hematologic malignancies.
Whole genome sequences discriminate hereditary hemorrhagic telangiectasia phenotypes by non-HHT deleterious DNA variation
Authors: Joyce Katie E. , Onabanjo Ebun , Brownlow Sheila , Nur Fadumo , Olupona Kike , Fakayode Kehinde , Sroya Manveer , Thomas Geraldine A. , Ferguson Teena , Redhead Julian , Millar Carolyn M. , Cooper Nichola , Layton D. Mark , Boardman-Pretty Freya , Caulfield Mark J. ,   Genomics England Research Consortium, Shovlin Claire L.
Published: March 2022

The abnormal vascular structures of hereditary hemorrhagic telangiectasia (HHT) often cause severe anemia due to recurrent hemorrhage, but HHT causal genes do not predict the severity of hematological complications. We tested for chance inheritance and clinical associations of rare deleterious variants in which loss-of-function causes bleeding or hemolytic disorders in the general population. In double-blinded analyses, all 104 patients with HHT from a single reference center recruited to the 100 000 Genomes Project were categorized on new MALO (more/as-expected/less/opposite) sub-phenotype severity scales, and whole genome sequencing data were tested for high impact variants in 75 HHT-independent genes encoding coagulation factors, or platelet, hemoglobin, erythrocyte enzyme, and erythrocyte membrane constituents. Rare variants (all gnomAD allele frequencies <0.003) were identified in 56 (75%) of these 75 HHT-unrelated genes. Deleteriousness assignments by Combined Annotation Dependent Depletion (CADD) scores >15 were supported by gene-level mutation significance cutoff scores. CADD >15 variants were identified in 38/104 (36.5%) patients with HHT, found for 1 in 10 patients within platelet genes; 1 in 8 within coagulation genes; and 1 in 4 within erythrocyte hemolytic genes. In blinded analyses, patients with greater hemorrhagic severity that had been attributed solely to HHT vessels had more CADD-deleterious variants in platelet (Spearman ρ = 0.25; P = .008) and coagulation (Spearman ρ = 0.21; P = .024) genes. However, the HHT cohort had 60% fewer deleterious variants in platelet and coagulation genes than expected (Mann-Whitney test P = .021). In conclusion, patients with HHT commonly have rare variants in genes of relevance to their phenotype, offering new therapeutic targets and opportunities for informed, personalized medicine strategies.
A multicenter prospective cohort study to evaluate feasibility of radio-frequency identification surgical guidance for nonpalpable breast lesions: design and rationale of the RFID Localizer 1 Trial
Authors: den Dekker Bianca M. , Christenhusz Anke , van Dalen Thijs , Jongen Lisa M. , van der Schaaf Margreet C. , Dassen Anneriet E. , Pijnappel Ruud M.
Published: March 2022

Background

Breast cancer screening and improving imaging techniques have led to an increase in the detection rate of early, nonpalpable breast cancers. For early breast cancer, breast conserving surgery is an effective and safe treatment. Accurate intraoperative lesion localization during breast conserving surgery is essential for adequate surgical margins while sparing surrounding healthy tissue to achieve optimal cosmesis. Preoperative wire localization and radioactive seed localization are accepted standard methods to guide surgical excision of nonpalpable breast lesions. However, these techniques present significant limitations. Radiofrequency identification (RFID) technology offers a new, nonradioactive method for localizing nonpalpable breast lesions in patients undergoing breast conserving surgery. This study aims to evaluate the feasibility of RFID surgical guidance for nonpalpable breast lesions.

Methods

This multicenter prospective cohort study was approved by the Institutional Review Board of the University Medical Center Utrecht. Written informed consent is obtained from all participants. Women with nonpalpable, histologically proven in situ or invasive breast cancer, who can undergo breast conserving surgery with RFID localization are considered eligible for participation. An RFID tag is placed under ultrasound guidance, up to 30 days preoperatively. The surgeon localizes the RFID tag with a radiofrequency reader that provides audible and visual real-time surgical guidance.

The primary study outcome is the percentage of irradical excisions and reexcision rate, which will be compared to standards of the National Breast Cancer Organisation Netherlands (NABON)(≤ 15% irradical excisions of invasive carcinomas). Secondary outcomes include user acceptability/experiences, learning curve, duration and ease of the placement- and surgical procedure and adverse events.

Discussion

This study evaluates the feasibility of RFID surgical guidance for nonpalpable breast lesions. Results may have implications for the future localization techniques in women with nonpalpable breast cancer undergoing breast conserving surgery.

Trial registration

Netherlands National Trial Register, NL8019, registered on September 12th 2019.
MiR-106b-5p regulates esophageal squamous cell carcinoma progression by binding to HPGD
Authors: Yang Fan , Sun Zhanwen , Wang Dengyun , Du Tian
Published: March 2022

Background

Several studies have documented the key role of microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Although the expression of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene and miR-106b-5p are reportedly linked to cancer progression, their underlying mechanisms in ESCC remain unclear.

Methods

mRNA and miRNA expression in ESCC tissues and cells were analyzed using RT-qPCR. Luciferase and RNA pull-down assays were used to identify the interaction between miR-106b-5p and HPGD. Xenograft and pulmonary metastasis models were used to assess tumor growth and metastasis. CCK-8, BrdU, colony formation, adhesion, cell wound healing, Transwell, and caspase-3/7 activity assays, and flow cytometry and western blot analyses were used to examine the function of miR-106-5p and HPGD in ESCC cell lines.

Results

The findings revealed that miR-106b-5p expression was upregulated in ESCC tissues and cell lines. miR-106b-5p augmented cellular proliferation, colony formation, adhesion, migration, invasion, and proportion of cells in the S-phase, but reduced apoptosis and the proportion of cells in G1-phase. Silencing of miR-106-5p inhibited tumor growth in vivo and pulmonary metastasis. Although HPGD overexpression suppressed proliferation, colony formation, adhesion, migration, and invasion of ESCC cells, it promoted apoptosis and caused cell cycle arrest of the ESCC cells. The results also indicated a direct interaction of HPGD with miR-106b-5p in ESCC cells. Furthermore, miR-106b-5p inhibited HPGD expression, thereby suppressing ESCC tumorigenesis.

Conclusion

Our data suggest that miR-106b-5p enhances proliferation, colony formation, adhesion, migration, and invasion, and induces the cycle progression, but represses apoptosis of ESCC cells by targeting HPGD. This suggests that the miR-106b-5p/HPGD axis may serve as a promising target for the diagnosis and treatment of ESCC.
Lack of tumorigenesis and protumorigenic activity of human umbilical cord mesenchymal stem cells in NOD SCID mice
Authors: He Jie , Yao Xiang , Mo Ping , Wang Kai , Yang Zai-ling , Tian Ni-ni , Zhu Xiang-qing , Zhao Jing , Pang Rong-qing , Ruan Guang-ping , Pan Xing-hua
Published: March 2022

Background

The tumorigenesis of infused umbilical cord mesenchymal stem cells (UC-MSCs) is being preclinically evaluated.

Methods

We observed tumor formation in NOD SCID mice after a single subcutaneous injection of hUC-MSCs and the effect of these cells on tumor growth in tumor-bearing mice. Three generations (P5, P7, and P10) of hUC-MSCs (1 × 107) from two donors (hUC-MSC1 and hUC-MSC2) were inoculated subcutaneously into NOD SCID mice. Subcutaneous transplantation models were established in NOD SCID mice with human cervical cancer HeLa cells (solid tumor) and human B cell lymphoma Raji cells (hematological tumor). Then, the animals were euthanized, gross dissection was performed, and tissues were collected. Various organs were observed microscopically to identify pathological changes and tumor metastasis.

Results

In the tumorigenesis experiment, no general anatomical abnormalities were observed. In the tumor promotion experiment, some animals in the HeLa groups experienced tumor rupture, and one animal died in each of the low- and medium-dose hUC-MSC groups. The results may have occurred due to the longer feeding time, and the tumor may have caused spontaneous infection and death. Pathological examination revealed no metastasis to distant organs in any group. In the Raji tumor model, some animals in each group experienced tumor rupture, and one animal in the medium-dose hUC-MSC group died, perhaps due to increased tumor malignancy. Thus, hUC-MSCs neither promoted nor inhibited tumor growth. No cancer cell metastasis was observed in the heart, liver, spleen, lungs, kidneys or other important organs, except that pulmonary venule metastasis was observed in 1 animal in the model group.

Conclusions

Injected hUC-MSCs were not tumorigenic and did not significantly promote or inhibit solid or hematological tumor growth or metastasis in NOD SCID mice.
Aqueous Thunbergia laurifolia leaf extract alleviates paraquat-induced lung injury in rats by inhibiting oxidative stress and inflammation
Authors: Palipoch Sarawoot , Punsawad Chuchard , Koomhin Phanit , Na-Ek Prasit , Poonsawat Wasinee , Kimseng Rungruedi , Chotipong Potiga , Bunluepuech Kingkan , Yusakul Gorawit , Suwannalert Prasit
Published: March 2022

Background

Paraquat (PQ) has been reported to have a high mortality rate. The major target organ of PQ poisoning is the lungs. The pathogenesis of PQ-induced lung injury involves oxidative stress and inflammation. Unfortunately, there is still no effective antidote for PQ poisoning. We hypothesized that aqueousThunbergia laurifolia(TL) leaf extract is a possible antidote for PQ-induced lung injury.

Methods

The total phenolic content and caffeic acid content of an aqueous extract of TL leaves were analyzed. Male Wistar rats were randomly divided into four groups (n = 4 per group): the control group (administered normal saline), the PQ group (administered 18 mg/kg body weight (BW) PQ dichloride subcutaneously), the PQ + TL-low-dose (LD) group (administered PQ dichloride subcutaneously and 100 mg/kg BW aqueous TL leaf extract by oral gavage) and the PQ + TL-high-dose (HD) group (administered PQ dichloride subcutaneously and 200 mg/kg BW aqueous TL leaf extract by oral gavage). Malondialdehyde (MDA) levels and lung histopathology were analyzed. In addition, the mRNA expression of NADPH oxidase (NOX), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) was assessed using reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of IL-1β and TNF-α was analyzed using immunohistochemistry.

Results

The total phenolic content of the extract was 20.1 ± 0.39 μg gallic acid equivalents (Eq)/mg extract, and the caffeic acid content was 0.31 ± 0.01 μg/mg. The PQ group showed significantly higher MDA levels and NOX, IL-1β and TNF-α mRNA expression than the control group. Significant pathological changes, including alveolar edema, diffuse alveolar collapse, hemorrhage, leukocyte infiltration, alveolar septal thickening and vascular congestion, were observed in the PQ group compared with the control group. However, the aqueous TL leaf extract significantly attenuated the PQ-induced increases in MDA levels and NOX, IL-1β and TNF-α expressions. Moreover, the aqueous TL leaf extract ameliorated PQ-induced lung pathology.

Conclusion

This study indicates that aqueous TL leaf extract can ameliorate PQ-induced lung pathology by modulating oxidative stress through inhibition of NOX and by regulating inflammation through inhibition of IL-1β and TNF-α expressions. We suggest that aqueous TL leaf extract can be used as an antidote for PQ-induced lung injury.