Biomarkers for colorectal cancer chemotherapy: Recent updates and future perspective.

During the last few decades, the treatment options available for patients with metastatic colorectal cancer (mCRC) have undergone continuous improvements, transitioning from conventional chemotherapy to targeted therapy. These therapeutic innovations have led to significant improvements in patient clinical outcomes. However, there remains a need to improve the outcome for many CRC patients. Chemotherapy remains a cornerstone of CRC treatment, but the wide variability in tumour response and adverse reactions to chemotherapy poses a challenge to cancer treatment management. As a result, there is an unmet need to identify predictive biomarkers of chemotherapeutic response to guide treatment decisions. In this review, we summarise the conventional biomarkers used to predict chemotherapy responses in CRC and provide an overview of emerging predictive biomarkers based on the current understanding of the molecular biology of treatment response. Finally, we explore the challenges and future prospects of biomarker discovery to improve the prediction of patient response and ensure optimal treatment management for patients with metastatic CRC.

Chiral Response of Twisted Bilayer Graphene.

We present an effective (minimal) theory for chiral two-dimensional materials. These materials possess an electromagnetic coupling without exhibiting a topological gap. As an example, we study the response of doped twisted bilayers, unveiling unusual phenomena in the zero frequency limit. An in-plane magnetic field induces a huge paramagnetic response at the neutrality point and, upon doping, also gives rise to a substantial longitudinal Hall response. The system also accommodates nontrivial longitudinal plasmonic modes that are associated with a longitudinal magnetic moment, thus endowing them with a chiral character. Finally, we note that the optical activity can be considerably enhanced upon doping and our general approach would enable systematic exploration of 2D material heterostructures with optical activity.

Oral Incompetence: changes in speech intelligibility following facial nerve paralysis.

BACKGROUND: Speech may be compromised following facial nerve paralysis (FNP), depending on the cause of the paralysis. This can result in lower quality of life and a reduced capacity to return to vocational roles. Despite its prevalence, it is incompletely understood and rarely described. This study prospectively evaluated the impact of FNP on speech intelligibility. METHODS: This observational study recruited patients who were diagnosed with FNP and who reported oral incompetence from the Sydney Facial Nerve Service. Their speech was analysed using patient reported outcome measures (Speech Handicap Index) and perceived intelligibility (Speech Pathologist, community member control participants, participant self-rating, and dictation software). RESULTS: Forty participants with FNP and 40 controls were recruited. Participants with FNP rated their intelligibility to be significantly worse than other raters (p <0.001). Consonant analysis demonstrated bilabial, fricatives and labiodental phonemes to be most commonly affected following FNP. CONCLUSION: Oral competence is compromised after FNP which can lead to a poorer perception of their intelligibility and reduced speech related quality of life.

Comparison between the radial forearm and superficial circumflex iliac artery perforator free flaps for oral soft tissue reconstruction.

The radial forearm free flap (RFFF) is widely used for oral reconstruction. The superficial circumflex iliac artery perforator (SCIP) flap is an increasingly utilized alternative. The cases of 165 patients who received either an RFFF or SCIP flap for oral reconstruction at Chris O'Brien Lifehouse, Sydney were reviewed. The aim was to report on patient, pathology, treatment, and outcome variables and to compare these between the two flap groups. A RFFF was used in 126 patients and a SCIP flap in 39 patients. SCIP flap patients were younger (P < 0.001) and had shorter operative times (P < 0.001), shorter anaesthetic times (P < 0.001), and more frequent recipient site dehiscence (P = 0.005) when compared to RFFF patients. The SCIP flap was significantly less frequently used for composite resections including bone when compared to the RFFF (P < 0.001). The primary site distribution was more even for RFFF patients (P < 0.001). There were no SCIP flap failures; three RFFF failures occurred. SCIP flaps performed comparably in terms of operative and clinical outcomes. Most SCIP flaps were utilized in younger patients with partial glossectomy defects.

Multicenter evaluation of an interdisciplinary 52-week weight loss program for obesity with regard to body weight, comorbidities and quality of life--a prospective study.

OBJECTIVES: To determine the effectiveness of a structured multidisciplinary non-surgical obesity therapy program on the basis of a temporary low-calorie-diet for 12 weeks, and additional intervention modules to enhance nutritional education, to increase physical activity and to modify eating behavior. DESIGN: Prospective multicenter observational study in obese individuals undergoing a medically supervised outpatient-based 52-week treatment in 37 centers in Germany. SUBJECTS: A total of 8296 participants with a body mass index (BMI) of >30 kg m(-2) included within 8.5 years. MEASUREMENTS: Main outcome measures were body weight loss, waist circumference (WC), blood pressure, quality of life and adverse events. RESULTS: In females, initial body weight was reduced after the 1-year-intervention by 19.6 kg (95% confidence intervals 19.2-19.9 kg) and in males by 26.0 kg (25.2-26.8) according to per protocol analysis of 4850 individuals. Intention-to-treat (ITT) analysis revealed a weight reduction of 15.2 kg (14.9-15.6) in females and 19.4 kg (18.7-20.1) in males. Overall, the intervention resulted in mean reduction in WC of 11 cm; it reduced the prevalence of the metabolic syndrome by 50% and the frequency of hypertension from 47 to 29% of all participants (ITT, all P<0.001). The beneficial effects could be documented for up to 3 years and comprised significant improvement of health-related quality of life. The incidence of adverse effects was low; the only event repeatedly observed and possibly related to either the intervention or the underlying disease was biliary disorders. CONCLUSION: The present non-surgical intervention program is a highly effective treatment of obesity grades I-III and obesity-related diseases, and therefore, could be a valuable basis for future weight maintenance strategies required for sustained success.

Deformation and scattering in graphene over substrate steps.

The electrical properties of graphene depend sensitively on the substrate. For example, recent measurements of epitaxial graphene on SiC show resistance arising from steps on the substrate. Here we calculate the deformation of graphene at substrate steps, and the resulting electrical resistance, over a wide range of step heights. The elastic deformations contribute only a very small resistance at the step. However, for graphene on SiC(0001) there is strong substrate-induced doping, and this is substantially reduced on the lower side of the step where graphene pulls away from the substrate. The resulting resistance explains the experimental measurements.

Disparity in female and Asian representation amongst cardiology journal editorial boards members: a call for empowerment.

BACKGROUND: While progress is evident in gender and ethnic representation in the workplace, this disparity remains prevalent in academic positions. OBJECTIVES: We examined gender and Asian ethnic representation in editorial boards of cardiology journals. METHODS: A cross-sectional analysis was conducted using publicly available data on Cardiology and Cardiovascular medicine journals in the first quartile of the 2020 Scimago Journal & Country Rank indicator. The proportions of female and Asian editorial board members, associate editors and editors-in-chief were assessed. Subgroup analyses were conducted based on the journal's geographical origin, subspecialty and demographic of the editor-in-chief. RESULTS: Seventy-six cardiology journals, involving 8915 editorial board members, were included. Only 19.6% of editorial board members were female, 20.8% Asians and 4.0% Asian females. There were less female representation amongst editors-in-chief (9.9%) compared to associate editors (22.3%). European (18.1%) and North American-based journals (21.1%) had higher female representation compared to Asian-based journals (8.7%). There was lower Asian representation in European (18.1%) and North American-based journals (19.9%) compared to Asian-based journals (72.3%). Females were underrepresented in interventional (14.5%) journals, while Asians were underrepresented in general cardiology (18.3%) and heart failure (18.3%) journals. Journals led by female editors-in-chief had significantly higher female representation compared to male-led ones, while journals with Asian editors-in-chief had greater Asian representation compared to non-Asian led ones. CONCLUSION: This study highlights the female and Asian ethnic underrepresentation in academic roles in cardiology journal editorial boards. Further analysis is needed for other ethnicities, while the community pushes towards gender-balanced and ethnic diversity across editorial boards.

The impact of radical parotidectomy with immediate facial nerve reconstruction: a quality-of-life measure.

OBJECTIVE: Immediate facial nerve reconstruction is the standard of care following radical parotidectomy; however, quality of life comparisons with those undergoing limited superficial parotidectomy without facial nerve sacrifice is lacking. METHOD: Patients who underwent parotidectomy were contacted to determine quality of life using the University of Washington Quality of Life and Parotidectomy Specific Quality of Life questionnaires. A total of 29 patients (15 in the radical parotidectomy and 14 in the limited superficial parotidectomy groups) completed and returned questionnaires. RESULTS: Using the University of Washington Quality of Life Questionnaire, similar quality of life was noted in both groups, with the radical parotidectomy group having significantly worse speech and taste scores. Using the Parotidectomy Specific Quality of Life Questionnaire, the radical parotidectomy group reported significantly worse speech, eye symptoms and eating issues. CONCLUSION: Those undergoing radical parotidectomy with reconstruction had comparable overall quality of life with the limited superficial parotidectomy group. The Parotidectomy Specific Quality of Life Questionnaire better identified subtle quality of life complaints. Eye and oral symptoms remain problematic, necessitating better rehabilitation and more focused reconstructive efforts.

The utility of postoperative radiotherapy in intermediate-risk oral squamous cell carcinoma.

The effectiveness of postoperative radiotherapy (PORT) in improving outcomes remains debatable for oral squamous cell carcinoma (OSCC) patients with pathological intermediate-risk factors (IRFs) after surgery. A retrospective analysis was conducted on 432 intermediate-risk OSCC patients defined by histological reporting of close margin (<5mm), early nodal disease (pN1), depth of invasion/tumour thickness ≥5mm, perineural invasion, and/or lymphovascular invasion. Outcomes measured were disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). PORT was associated with an improvement in 5-year DFS on univariable analysis (80% vs 71%; P=0.044), but this did not remain significant on multivariable analysis. PORT was not associated with differences in DSS or OS. The surgical salvage rate was similar in the PORT and surgery-only groups (41% vs 47%; P=0.972). Perineural invasion was found to be an independent predictor of inferior DSS (hazard ratio (HR) 2.19), DFS (HR 1.89), and OS (HR 1.97). Significantly worse outcomes were observed for patients with ≥4 concurrent IRFs. The application of PORT was associated with lower rates of recurrence, but the benefit was less apparent on mortality. Patients with perineural invasion and multiple concurrent IRFs were found to be at greatest risk, representing a subset of intermediate-risk OSCC patients who may benefit from PORT.

Massive Tibial Bone Regeneration with Autologous Peripheral Blood Stem Cells using Ilizarov Bone Transport: A Case Report.

This is a case report of a Gustilo-Anderson Type IIIB comminuted open right tibial fracture with massive bone loss, complicated by methicillin-resistant Staphylococus aureus (MRSA) infection. Non-viable and contaminated bony fragments were removed and infected bone resected. Soft tissue coverage and antibiotics were effective against the MRSA infection. A unifocal bone transport with the Ilizarov method regenerated 13cm of the missing tibia. Autologous peripheral blood stem cells (PBSC) injections into the osteogenesis site boosted bone regeneration and consolidation with a shortened Bone Healing index (BHI) of 23 days/cm.

Elective neck dissection versus observation for early-stage oral squamous cell carcinoma: Systematic review and meta-analysis.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the seventh most common cancer globally, and has been identified as a growing health concern. This study aims to evaluate the current literature comparing elective neck dissection to observation in the treatment of early-stage tongue SCC, focusing on nodal recurrence, overall survival, disease specific survival statistics from randomised controlled trials comparing the two interventions. METHODS: Systematic review and meta-analysis was conducted according to PRISMA guidelines. The odds ratio (OR) was used as a summary statistic. RESULTS: From 8 studies, there was a total of 372 cases of recurrence, 98 (15.1%) in END group and 274 (41.5%) in the Observation group. There was a significantly lower rate of recurrence in the END group compared to observation (OR 0.25, 95% CI 0.16-0.39, I2 = 54%, P < 0.00001). END was associated with higher overall survival rates when compared with observation (OR 1.95, 95% CI 1.40-2.73, I2 = 14%, P < 0.0001). END was also associated with higher disease-specific survival compared with observation (OR 1.88, 95% CI 1.21-2.93), I2 = 47%, P = 0.005), with no significant heterogeneity noted. CONCLUSIONS: END was associated with significantly lower recurrence rates and higher overall and disease-specific survival compared to a conservative observation approach in early-stage oral SCC with clinically N0 neck.

Structure, function, and evolutionary relationships of Fc domains of human immunoglobulins A, G, M, and E.

Human immunoglobulins, A, G, M, and E have strong homology in amino acid sequence (about 30 percent) distributed nonuniformly throughout the Fc region. Immunoglobulins M are A are least alike in the first Fc domain and most alike in the second. Individual domains of heavy chains have evolved with different mutation rates but with conservation of essential structural features. No relation of primary structure to complement binding ability is apparent.

Complete covalent structure of a human IgA1 immunoglobulin.

The complete covalent structure has been determined for a human myeloma IgA1 immunoglobulin. This protein has unique features in the amino acid sequence and disulfide bridge structure of the variable (V) and constant (C) regions of both the alpha heavy and the lambda light chains, and in the number and loci of oligosaccharides. Whereas C region domains of heavy chains have evolved independently over eons, recent isotypic variations have occured in lambda light chains and possibly in alpha heavy chains.

Thymosin stimulates secretion of luteinizing hormone-releasing factor.

Partially purified thymosin fraction 5 and one of its synthetic peptide components, thymosin beta 4, but not thymosin alpha 1, stimulated secretion of luteinizing hormone--releasing factor from superfused medial basal hypothalami from random cycling female rats. In addition, luteinizing hormone was released from pituitary glands superfused in sequence with hypothalami. No release of luteinizing hormone in response to thymosin was observed from pituitaries superfused alone. These data provide the first evidence of a direct effect of the endocrine thymus on the hypothalamus and suggest a potentially important role for thymic peptides in reproductive function.

Panton Valentine leukocidin MSSA leading to multi-organ failure.

We report a case of a 15-year-old boy who developed multiple organ failure secondary to a sport injury leading to infection with a Panton Valentine Leukocidin (PVL) secreting Community-Acquired Methicillin Sensitive Staphylococcus Aureus (CA MSSA). Aggressive antibiotic therapy eventually led to recovery.

Ground-Breaking Innovations in General Psychology.

The article addresses two recently published books in General Psychology by Niels Engelsted and Jens Mammen. The two approaches offer in their own way solutions to the so-called 'crisis of psychology'. Mammen's new logical foundation for psychology is based on two different properties of the objects we relate to: those characterizing the objects appearances, and those characterizing the objects as unique substances or singulars distributed in time and space - the existence of the objects as opposed to the appearance of the objects. Engelsted makes a journey from Aristotle (384-322 BC) until today's psychology in his quest to identify the domain of psychology. He places the psyche in the natural world as a result of locomotion in the first, most simple animal life. The domain of psychology includes intentionality, mind and consciousness.

Effects of different surface modification and contents on municipal solid waste incineration fly ash/epoxy composites.

Incineration fly ash, a waste from municipal solid waste incineration plant can be used to replace conventional filler as reinforcing filler to enhance the mechanical strength of a composite. Surface modification was performed on the incineration fly ash before mixing into the soft polymer matrix so as to improve interfacial bond of the filler and epoxy resin. In this study, detailed characterisation of mechanical, morphological and leaching behaviours of municipal solid waste incineration (MSWI) fly ash infused composite has been carried out. Flexural and tensile test was conducted to determine the effect on mechanical properties of the composite by varying the concentration of incineration fly ash filler added into polymer matrix and surface modification of incineration fly ash filler using silane coupling agent and colloidal mesoporous silica (CMS). The results indicated that composite infused with incineration fly ash filler surface treated with CMS shown improvement on the tensile and flexural strengths. In addition, SEM images showed that surface modification of incineration fly ash with colloidal mesoporous silica enhanced the interfacial bonding with polymer resin which explained the improvement of mechanical strength. Leaching test showed result of toxic metals such as Pb, Zn, Fe, Cu, Cr, Cd and Rb immobilised in the polymer matrix of the composite. Hence, the use of MSWI fly ash as reinforcing filler in the composite appears green and sustainable because this approach is a promising opportunity to substitute valuable raw material with MSWI fly ash.

Spontaneous intrathyroidal hematoma causing airway obstruction: A case report.

INTRODUCTION: Spontaneous thyroid hemorrhage is a rare occurrence that results in pain, discomfort, and occasionally compressive symptoms. Infrequently, extensive thyroid hemorrhage can result in a rapidly expanding hematoma resulting in airway compromise. This is a case of an otherwise healthy young woman, 3 months postpartum, with a slowly expanding spontaneous thyroid hemorrhage that measured at 7 × 5.5 × 5 cm by computed tomography. She ultimately required intubation to manage respiratory distress and subsequently a hemithyroidectomy for definitive treatment. The case presentation is followed by a literature review where known etiologies of thyroid hematoma including traumatic and nontraumatic causes, precipitating anticoagulation, and spontaneous rupture of branches of the external carotid artery are outlined. The potential links to pregnancy are explored. The roles of bedside thyroid ultrasound in the emergency department and lateral neck roentgenogram in diagnosis are explored. The importance of airway management and indications for conservative versus surgical treatments are discussed. CONCLUSIONS: This is a case of a spontaneous intrathyroidal hemorrhage, which progressed over days to ultimately cause airway compromise. It is imperative that physicians are educated on the appropriate detection and management of the potentially life-threatening spontaneous thyroid hematoma.