bluuebunny/crossref_metadata_2025 huggingface dataset:
An analysis of characteristics and content of highly used books for the general population in the cancer space on Amazon.com.
Authors: O'Keefe Ryan M , Keaveny Caitlin E. , Vesey Alicia M. , Jordan Mackenzie R. , Hamilton Grace A. , Letendre Nicole B. , Santiago Simonai E. , Hill-Kayser Christine E.
Published: June 2021

e24034

Background: Cancer patients and supporters frequently turn to written resources for assistance and empowerment in decision-making. Previous work has analyzed misinformation available on search and social media platforms; however, little attention has been paid to amazon.com (AMZ) despite 37% of cancer patients seeking information from books. Previous work also suggests there is a preponderance of vaccine-hesitant books on AMZ. Here, we report the first analysis of the characteristics and content of books, excluding medical textbooks, in the cancer space. Methods: On 11/25/20, the top 100 books were pulled from the “Best Sellers in Cancer” (BS) page on AMZ. Queries were also performed using keywords “cancer treatment” (CT), and “natural cancer treatment” (NCT), filtering for books. Non-sponsored results from the first 5 pages per search were pulled. 2 coders were trained to manually collect variables on genre, advice, terminology (TN) in the description, author, and publisher; disagreement was settled by a third coder. Books were excluded if they were not in English, duplicates within the same query, did not focus on human cancer, or were medical textbooks. Chi square testing was used to compare results of CT v. NCT. Analysis was performed using R software. Results: 56, 60, and 70 books were included for BS, CT, and NCT, respectively. For BS, 15 (26.8%) were memoirs, 12 (21.4%) dietary guides, 11 (19.6%) treatment guides, 6 (10.7%) self-help, and 4 (7.1%) cookbooks. 16 (28.6%) focused on one tumor subtype; breast was the most common (9, 56.3%). Many appeared to offer non data-driven advice (Table). Many BS books employed “war” TN (ex: fight, battle), “hype” TN (ex: game-changing), spiritual TN (ex: faith, God, prayer), and CAM TN (ex: supplement, herb) (Table). Many also insinuated offering a cure, or a novel therapy (Table). Compared with CT books, NCT books were more likely to offer non-data driven advice and be published independently, and less likely to have an MD/DO author (Table). Conclusions: Nonscientific advice is present in many non-medical text cancer books available on AMZ, including BS books. Patients seeking information on AMZ about NCT are likely to find books offering non-data driven advice or that insinuate a cure or new/novel information. Future work should investigate opportunities to regulate such content or to direct patients towards high-quality resources on platforms like AMZ.[Table: see text]
Patient-reported barriers to online meetings: The case of a myeloma support group in western Kenya in the era of COVID-19.
Authors: Oduor Mercy , Manyega Kelvin , Lotodo Therese , Okuku Austin , Namaemba Diana , Oyolo Lorraine , Oguda John , Vik Terry A.
Published: June 2021

e24036

Background: Multiple myeloma is a chronic progressive disease that calls for extended survivorship support post-diagnosis. Pre- COVID-19, the AMPATH Multiple Myeloma Program had created support groups for myeloma survivors and their caregivers that regularly met for health education, emotional support, and social opportunities. With the enforcement COVID-19 prevention and control protocols physical support group meetings became impossible. The program shifted to the online platform to sustain peer to peer support for myeloma patients and caregivers. We aim to describe challenges faced with online patient support group meetings as this has not been well documented in a resource-constrained setting. Methods: Myeloma patients and caregivers at Moi Teaching and Referral Hospital were contacted and a meeting date and time agreed. Participants were briefed on how to download and operate the zoom application in preparation for online meetings. A meeting link was shared with the expected attendees and a reminder sent two days before a meeting. Support group meetings were held for different groups among them myeloma survivors and caregivers. The meeting sessions were led by healthcare professionals – hematology consultants, social workers, nutritionist and psychosocial counsellors. Peer-to-peer sessions were also held. Results: Six online meeting sessions were held between June 2020 and December 2020. A total of 199 participants were expected to join the six different meetings but a low meeting turn-out of 25.6% was experienced. Participants were later contacted to unravel the reasons for a low turn-out. A total of 129 participants were contacted of which 88 responded. Out of the 88 respondents, 29% reported a tight work schedule, 25% short time meeting alerts, 20% did not have access to smartphones, and 8% had poor internet connectivity and another 8% reported no internet data bundles to connect to the internet. Conclusions: Low attendance of online meetings was observed. Participants cited scheduling and internet access as major obstacles to attending online support group meetings. Improved access to the internet through smartphones, reliable internet connection, and affordable data are needed in underserved communities to fully unlock the benefits of virtual platforms namely cost savings and effective information sharing.
Assessment of chemotherapy-induced cognitive impairment: A prospective study of the biochemical and metabolic effects of platinum/taxane-based chemotherapy in gynecologic cancer patients.
Authors: Hutchcraft Megan Leigh Gleason , Anderson-Mooney Amelia J , Dressler Emily Van Meter , Butterfield D. Allan , St. Clair Daret , Powell David K. , Koehl Lisa , Schmitt Frederick A. , Shelton Brent , Gorski Justin W. , Baldwin Lauren Ashley , DeSimone Christopher Philip , Gallion Holly H. , Ueland Fredrick R. , Miller Rachel W.
Published: June 2021

e24051

Background: Chemotherapy-induced cognitive impairment (CICI) is a common side effect of cancer therapy, affecting up to 75% of cancer patients. Oxidative stress is thought to play a key role in CICI and patients who have been treated with chemotherapy have demonstrated biochemical brain changes on magnetic resonance spectroscopy (MRS). Methods: Following institutional review board approval, chemotherapy-naïve gynecologic cancer patients scheduled to receive intravenous platinum/taxane-based chemotherapy were identified. The primary objective of this study was identification of chemotherapy-induced cognitive function changes using the Montreal Cognitive Assessment (MoCA) tool. This exploratory analysis evaluates correlations between changes in MoCA scores, oxidative analytes TNF-a, protein carbonyls (PC), and 4-hydroxynonenal (HNE) protein adducts, and MRS metabolic signals. Testing was performed at baseline and three weeks post-treatment. Simple linear regression was performed to evaluate the correlation between changes in MoCA scores and oxidative metabolites. Results: Fourteen patients were enrolled. Six patients had complete pre/post oxidative stress data, and four patients had complete pre/post MRS data. Five of six had decreased PC values (mean net change -15.17%, SD 0.15), half had increased HNE levels (mean net change +16.38%, SD 0.38), and four of six had decreased TNF-a values (mean net change -15.10%, SD 0.27) (Table). MoCA scores were positively correlated with serum PC levels ( r = 0.86, p = 0.03) and not significantly correlated with TNF-a or HNE levels. Of those with complete pre/post MRS data, all patients had a decrease in glycerophosphocholine + phosphocholine/creatinine ratio signals. MoCA raw score prior to and after completion of chemotherapy. A higher score indicates improved test performance. Positive percentage of oxidative stress markers (PC, HNE, TNF-a) indicates increased post-therapy levels compared to pre-therapy. Conclusions: In this study, we evaluated candidate oxidative stress serum markers and changes in MRS metabolite signals for CICI. Serum PC levels correlate with cognitive screening scores. For patients undergoing brain imaging, MRS evaluation for individual choline components, glycerophosphocholine and phosphocholine, may serve as an additional marker of oxidative damage. This pilot study highlights the potential value of serum PC levels and dedicated brain imaging for signs of oxidative stress, including MRS, to guide future CICI identification studies. Clinical trial information: NCT03324945. [Table: see text]
Prevalence of advance care planning in a resident run clinic in an underserved community.
Authors: Alexander Swetha Ann , Mathew Thomas Vinay , Wu David , Kulkarni Radhika , Rabitaille William
Published: June 2021

e24067

Background: Advance Care Planning (ACP) ensures that patients receive care that is in line with their values and preferences. ACP is best done in the outpatient setting. Despite recognizing the importance of ACP, the rates of ACP completion continue to be low. We conducted a retrospective study to determine the rates of ACP in a resident run primary care clinic in Hartford, Connecticut, which serves the underserved community. We looked at patient characteristics to find correlation with ACP completion. We also aimed to determine the reasons which could decrease the completion of ACP. Methods: This was a retrospective chart review. Patients who met any of the inclusion criteria [i) Age>65 ii) End stage renal disease on dialysis iii) Metastatic/Recurrent cancer iv) End stage heart failure v) COPD Gold stage D] and were seen in the primary care clinic from September 1, 2019 to December 31, 2019 were selected. Their charts were reviewed to see if ACP was documented during primary care visits over the past two years. The demographics of the patients were noted. Subsequently, a survey was distributed to residents to determine the possible causes of low rates of ACP discussion. Results: The characteristics of the 373 patients included in the study are shown in Table 1. Only 14 (3.8%) of the 373 had documentation of ACP during their primary care visits. The characteristics of the 14 patients in whom ACP was done are as follows: Sex- Female 9/14 (64%); Ethnicity- Hispanic 10/14 (71%), African American 4/14 (29%); Religious Affiliation- Christian 13/14 (93%), None 1/14 (7%); Married/Partner 2/14 (14%). Patient demographics including sex (p 0.6), religious beliefs (p 0.8), and marital status (p 0.6) did not show any correlation with the likelihood of ACP completion. Of the 31 residents who answered the survey, the most commonly listed barriers to ACP completion were the following: lack of time to conduct these discussions (94%), forgetting to conduct ACP discussions (48%), and lack of training (19%). All the residents believed that ACP discussion was beneficial to patients and medical providers. Conclusions: The rates of ACP planning in our clinic are much lower than the national average. African American and Hispanics, who make up the majority of our clinic population, traditionally have had low rates of ACP completion. This is an important issue that needs to be addressed. Advance care planning training should be also be strengthened during residency. [Table: see text]
Overall survival (OS) and prognostic factors (PF) of patients (pts) with metastatic solid tumors admitted in intensive care unit (ICU).
Authors: Hautecloque-Raysz Segolene , Albert Thananayagam Marie , Martignene Niels , Le Deley Marie-Cecile , Penel Nicolas , Carnot Aurelien
Published: June 2021

e24074

Background: Admission of cancer pts in ICU is a medical and ethical challenge, since there is no reliable prognostic tool for guiding decision making. Therefore, recent progress in cancer management improved the OS of advanced cancer pts, rendering this issue more and more frequent. Methods: We have retrospectively analyzed the medical charts of 129 consecutive pts treated in our institution and admitted in ICU from 01/2014 and 04/2019. We identified PF using Cox Models. We analyzed PF for OS or for ability to restart systemic treatment. Results: At the time of ICU admission, the mean age was 58.9 (range, 25-81). The were 51% of men. PS were 0-1 in 61% and 2-3 in 39%. The most prevalent cancers were lung (20%), sarcoma (17%), breast (16%) and gynecological cancers (11%). The number of metastatic sites was 1 (17%), 2 (39%), 3 (26%) and more (19%). The malignancy was stable in 69% and progressive in 31%. Pts currently received systemic treatment in 78%, were free of treatment in 5% and were not yet treated in 16%. Cancer itself (53%), toxicity of treatment (43%) and underlying comorbidities (37%) contributed to ICU admission. The number of organ failures was 0 in 12%, 1 in 40%, 2 in 26% and 3 or more in 22%. The 4 most symptoms were dyspnea (34%), severe infection (25%), cardiac event (23%) and bleeding (10%). Pt management required vasoamines administration (38%), ventilation (31%) and dialysis (4%). The median duration of stay in ICU was 4 days (range, 0-71). 21 (16%) pts died in ICU and 16 (12%) just after ICU discharge. 83 pts returned to home (64%). Systemic treatment was done in 61% of pts who left hospitalization alive after ICU. 1-month, 6-month and 12-month OS were 67, 36 and 21%, respectively. Multivariate analysis identified the following PF for OS: PS = 0 (HR = 0.57 [0.38-0.79]; p = .007), admission related to underlying comorbidity (HR = 0.63 [0.41-0.98], p = .0001) or admission related to treatment toxicity (HR = 0.31 [0.17-0.56] p = .0001). Multivariate identified 1 PF for ability to restart systemic treatment: one or less organ failure (HR = 0.34 [0.14-0.83], p = 0.02). Conclusions: In ICU, OS of adult pts with solid tumors looks like the non-cancer population. ¼ of admitted pts died in ICU or just after. Key PF were PS and cause of critical state. When ICU admission is related to cancer itself, the prognosis was poor.
A cross-sectional study on effectiveness of antiemetic regimens for chemotherapy-induced nausea and vomiting: A single-center retrospect study of 1,000 patients.
Authors: Cong Luo , Shang Mingge , Chen Lei , Qi Xu , Jingjing Li , Wei Qing , Ying Jieer
Published: June 2021

e24100

Background: Chemotherapy-induced nausea and vomiting (CINV) is a common symptom in patients who undergoing chemotherapy, it is very important to control CINV to maintain dose intensity and patients' quality of life. To analyse the current situation of CINV for the tumor patients who undergoing chemotherapy, we used a cross-sectional survey to assess CINV status in those patients, and whether the drugs used by doctors in each department met the guidelines, and compared the efficacy of different antiemetic regimens on acute and delayed CINV overall post-chemotherapy periods. Methods: 1,000 patients were randomly selected from 5,468 patients with chemotherapy discharged from different departments of Zhejiang cancer hospital in China between April 1 and April 30, 2019, and there were 87 responses totally. Medical records were collected on patient’s department (internal medicine, surgery, radiotherapy, interventional), chemotherapy regimens, anti-vomiting program, etc. Patients' feedbacks were recorded by CTCAE4.03 standard using MASCC antiemetic tool (Mat). Participants reported the frequency, severity, and impact on daily life of CINV from the day of chemotherapy administration up to 5 days thereafter and nausea and vomiting, as well as pharmacologic and chemotherapy used. Results: A total of 66 antineoplastic drugs were investigated, of which 52 were given intravenously and 14 orally.There were 9, 7, 50 drugs with high, moderate and low emetic risk respectively.The most prescribed prophylactic regimens for the management of CINV were aprepitant, 5-HT3R, H1-RA and dexamethasone and metoclopramide. The overall incidence of CINV were 44.34%, 24.57% and 39.66% patients reported nausea or vomiting in the acute and delayed phases. 19.89% patients had both acute and delayed CINV. The consistency rate of antiemetic with guideline was 63.19% in internal medicine department, 61.41% in surgery department and 52.91% in radiotherapy department, which showed a significant gap between the actual use of drugs and the recommended guidelines(P = 0.001). In 875 patients, 518 patients received guideline recommended antiemetic regimen, the CINV rates of complete response (CR), defined as no vomiting with no rescue medication, were 61.58%. While the CR rates in other 357 patients were 47.06%(P < 0.001). Nausea was more frequent across the overall observation period (43.77% VS 18.86%). However, vomiting was more sever and had a greater impact on life than nausea. Conclusions: Overall, adherence to the guideline recommendations in different departments were poor with varying degrees. Future studies should set hard outcomes, such as the absence of any symptoms, as a primary end point. The standardized management of CINV in patients need to be further strengthened and doctors need to use drugs more regularly to reduce the occurrence of CINV in patients.
A phase II study to evaluate the safety and efficacy of OQL011 on VEGFR inhibitor-associated hand-foot-skin reaction in cancer patients.
Authors: Lacouture Mario E. , Anadkat Milan J. , Marathe Omkar Subhash , Vogelzang Nicholas J. , Lam Elaine Tat , Kaffenberger Benjamin , Choi Jennifer N. , Webb Mark L. , Tyler Robert Claude , Ju Juegang , Tang Hong , Luo Jie , Patel Anisha
Published: June 2021

TPS12132

Background: Hand-Foot Skin Reaction (HFSR) is frequently associated with the use of multi-targeted tyrosine kinase inhibitors of the vascular endothelial growth factor receptor (VEGFRi) such as cabozantinib, regorafenib, sunitinib, and lenvatinib. HFSR affects the skin on the palms and soles and is manifested as edema, erythema, hyperkeratosis, and bullae, leading to a decrease in quality of life and interruptions in dosing. The incidence of HFSR differs among VEGFRi, ranging from 5-60% (all grades) and 1-18% (grade 3). To date, there is no FDA approved treatment for HFSR, and marginal benefit has been shown with topical urea or steroids. Although not fully elucidated, the pathogenesis of HFSR has been associated with impaired vascular repair mechanisms, caused by inhibition of VEGF signaling pathways. We hypothesize that topical stimulation of VEGFR through OQL011 will decrease the severity of HFSR symptoms via local upregulation of the VEGF/VEGFR related signaling pathways. Methods: NCT04088318 is a phase 2, double-blind, randomized controlled trial to evaluate the safety and efficacy of OQL011 compared to vehicle control in the treatment of moderate to severe HFSR in patients on VEGFRi therapy. Eligible patients will have ≥ grade 2 palmar plantar erythrodysesthesia (PPE). The study is expected to enroll 112 patients in two parts. In the first part, 42 patients will apply 0.2% OQL011 topical ointment or vehicle control (2:1 randomization) TID for six weeks. In Part 2, 70 subjects will be randomized into two additional dose levels or vehicle control in a 2:2:1 ratio. The two dose levels selected will be based on the efficacy and safety results of Part 1. The primary efficacy endpoint is improvement of NCI CTCAE v5.0 PPE to grade ≤1 by week 3. Photographs of the affected areas will be taken at Day 0, 7, 14, 21 and 42 timepoints. Superiority test will be performed to compare treatment groups, and the exposure-response relationship will be explored. In addition, an investigator global assessment (IGA) for HFSR will be used in this trial to specifically assess skin recovery and is proposed to be a new evaluation tool. The validity of IGA criteria will be evaluated by assessing the inter-rater and intra-rater reliability. The correlation between IGA, NCI CTCAE v5.0 for PPE, and patient reported outcomes including Visual Analog Scale of Pain, Hand-foot Quality of Life questionnaire will also be evaluated. This study began enrolling patients in December 2019 and is ongoing. Clinical trial information: NCT04088318.
Randomized double-blind, placebo-controlled study of topical diclofenac in prevention of hand-foot syndrome in patients receiving capecitabine.
Authors: Batra Atul , Santosh Akhil P. , Pramanik Raja , Gogia Ajay , Pandey R. M. , kumar akash , Sharma Atul
Published: June 2021

TPS12135

Background: The pathophysiology of capecitabine induced hand-foot syndrome (HFS) includes activation of cyclooxygenase (COX)-2, leading to an upregulation of the inflammatory cascade. Prophylaxis with oral celecoxib was previously reported to be associated with a significantly lower frequency of HFS (grade 1 [29.0% vs. 72.0%, p < 0.001] and grade 2 [11.8% vs. 30.0%, p=0.024]) (1). The findings were confirmed in a phase III trial (2). However, the associated systemic adverse events limit routine prophylactic use. Till date, no clinical trials have assessed the role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in preventing HFS. Methods: In this investigator-initiated randomised phase III double-blind, placebo controlled, parallel group trial, a total of 264 patients with any stage breast or gastrointestinal cancer planned to receive capecitabine as a single agent or in combination with other chemotherapy will be randomised (1:1) to 1% topical diclofenac or placebo (base for 1% topical diclofenac) arm at a single tertiary care cancer centre in India. Randomization will be done by stratified (male vs female, and capecitabine mono therapy vs combination) permuted block method using a computer generated random sequence and allocation concealment will be done by using sealed opaque envelopes. In both the arms, patients will be asked to apply 1 fingertip unit (FTU) of topical medication on both surfaces of bilateral hands twice daily for a total duration of 12 weeks or till development of grade 2 or higher HFS, whichever is earlier. The primary objective is to compare the effect of topical diclofenac with placebo in preventing clinically significant HFS (incidence of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 2 or higher HFS). The secondary objectives include comparison of topical diclofenac with placebo on (i) incidence of NCI CTCv5.0 all grade HFS, (ii) time to develop grade ≥2 HFS from start of capecitabine, (iii) patient-reported outcomes using HFS-14 questionnaire (iv) adherence with topical application using self-reported adherence diary, (v) capecitabine dose reductions, delays and cessation due to HFS and (vi) safety profile (NCICTCv5.0). The tertiary correlative endpoint is to correlate the occurrence and severity of HFS with serum COX-2 levels and polymorphism of dihydropyrimidine dehydrogenase (DPPD) enzyme. The trial is registered at the Clinical Trial Registry of India (CTRI/2021/01/030592). Till date, we have enrolled 12/264 patients. (1) Zhang RX et al. J Cancer Res Clin Oncol. 2011;137(6):953-957. (2) Zhang RX et al. Annals of oncology. 2012;23(5):1348-1353. Clinical trial information: CTRI/2021/01/030592.
A phase I study of AK119, an anti-CD73 monoclonal antibody, in combination with AK104, an anti-PD-1/CTLA-4 bispecific antibody, in patients with advanced or metastatic solid tumors.
Authors: Markman Ben , Hsieh Amy Hsin-Chieh , Coward Jermaine , Carlino Matteo S. , Frentzas Sophia , Jin Xiaoping , Li Baiyong , Wang Zhongmin Maxwell , Kwek Kon Yew , Xia Yu
Published: June 2021

TPS2675

Background: AK119 is a humanized IgG1 monoclonal antibody (mAb) that selectively binds to and inhibits the ectonucleotidase activity of CD73, a cell surface enzyme that converts adenosine monophosphate (AMP) into adenosine. Adenosine has been shown to facilitate tumor-mediated evasion. CD73 inhibition may therefore reduce adenosine accumulation and promote anti-tumor immunity. AK104 is a recombinant humanized IgG1 bispecific antibody that simultaneously binds to programmed cell death protein 1 (PD-1) and cytotoxic T- lymphocyte-associated antigen protein 4 (CTLA-4). Preliminary data from phase I and II studies suggest that AK104 has encouraging anti-tumor activity in selected tumor types and an improved safety profile compared to the co-administration of anti-PD-1 plus anti-CTLA-4 mAbs. Preclinical studies show that CD73 inhibition synergistically increases the anti-tumor activity of PD-1 and CTLA-4 immune checkpoint inhibitors (ICIs). Published early clinical data suggests that anti-CD73 therapy in combination with ICIs produces improved clinical outcomes. Thus, AK119 plus AK104 is postulated to have synergistically enhanced anti-tumor activity compared to the administration of anti-CD73 monotherapy or ICIs alone. Methods: This is a phase 1a/1b, first-in-human, multicenter, open-label study in patients with advanced solid tumors that are refractory to standard therapies. The primary objective is to assess safety, tolerability and dose limiting toxicity; and to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of AK119 in combination with AK104. Secondary objectives are to evaluate antitumor activity, PK and AK119 immunogenicity. The dose-escalation phase will evaluate 5 dose levels of AK119 (1mg/kg to 40 mg/kg Q2W IV) in combination with 6mg/kg AK104 Q2W IV using a 3+3+3 study design. Eligible pts will receive a single dose of AK119 on C0D1 of a 14-day “lead-in” period. Thereafter, from C1D1 pts will receive AK119 in combination with AK104 on a 28-day cycle, until unacceptable toxicity, confirmed progressive disease, subject withdrawal, or for a maximum of 24 months. The “lead-in” period is only applicable for dose-escalation cohorts. Any dose-escalation cohort not exceeding the MTD may be expanded to a maximum of 18 subjects with selected solid tumor types for further evaluation of safety, PK/ PD, immunogenicity, and preliminary anti-tumor activity. Cohort 1 is currently in progress with the first patient enrolled in January 2021. For the dose-expansion phase, cohorts of pts with advanced/metastatic pancreatic cancer or MSS/pMMR colorectal cancer will be enrolled. Cohorts of other tumor types may be added based on emerging pharmacodynamic and anti-tumor response data. Clinical trial information: NCT04572152.
A phase II open-label study of cpi-613 in combination with modified (m)FOLFIRINOX in patients with locally advanced pancreatic cancer.
Authors: Bajor David Lawrence , MOHAMED AMR , Selfridge J. Eva , Anderson Erin E. , Hardacre Jeffrey , Ammori John Brian , Lee Richard T. , Saltzman Joel N. , Winter Jordan Michael
Published: June 2021

TPS4176

Background: For patients with locally advanced pancreatic cancer, neoadjuvant trials are the preferred strategy. The goals of neoadjuvant treatment are to diminish the size of the primary tumor to allow for safe surgical resection and to limit the chance of developing metastatic disease. mFOLFIRINOX is the gold-standard for treatment in the adjuvant setting and an acceptable regimen in the neoadjuvant setting with many ongoing neoadjuvant trials using it as a chemotherapeutic backbone. CPI-613 (devimistat) is a small-molecule inhibitor of pyruvate dehydrogenase and alpha-ketogluterate dehydrogenase that has been studied in combination with mFOLFIRINOX in a phase I trial of patients with metastatic pancreas cancer and shown to be safe at the proposed phase II dose. Methods: This is a single-center, single-arm phase II trial for patients with locally advanced pancreatic cancer; defined as either borderline resectable or unresectable according to NCCN guidelines and interpreted by the primary investigator. Patients with metastatic disease are excluded. Patients will receive treatment with CPI-613 and mFOLFIRINOX per the table below. The primary endpoint is overall survival. Secondary endpoints are progression free survival and resection rate. At the time of submission this study has completed initial accrual with 37 patients enrolled. Clinical trial information: NCT03699319. [Table: see text]
BRAFMutations as Actionable Targets: A Paradigm Shift in the Management of Colorectal Cancer and Novel Avenues
Authors: Sahin Ibrahim Halil , Klostergaard Jim
Published: June 2021

BRAF mutations in colorectal cancer have been studied over the past several decades. BRAF V600E mutation, a class I mutation, is the most common oncogenic BRAF alteration in colorectal cancer. Until recently, the BRAF V600E mutation was not among actionable genes for colorectal cancer. However, recent discoveries have revealed therapeutic opportunities. The BRAF with or without MEK inhibition combined with epidermal growth factor receptor–directed therapy was recently found to be an effective therapy choice for patients with advanced-stage BRAF V600–mutant colorectal cancer. However, it is essential to distinguish patients with BRAF V600E–mutant mismatch repair–deficient colorectal cancer from those with mismatch repair–proficient colorectal cancer, as immune checkpoint inhibitor therapy is more appealing in this subset of patients with colorectal cancer. This review article discusses the molecular characteristics of class I, II, and III BRAF mutants and their impact on the clinical behavior of colorectal cancer. We also review the recent progress in the targetability of BRAF mutations in colorectal cancer, which has led to changes in clinical practice and elaborates on innovative therapeutic approaches to enhance the efficacy of BRAF-targeting therapies, to achieve more durable responses.
Social egg freezing
Authors: Winter George F
Published: June 2021

George F Winter takes a look at the evolving landscape of modern pregnancy options and what it means for women
An update on travel and COVID-19: what the practice nurse needs to know
Authors: Gawthrop Mary
Published: June 2021

Lockdown and international travel restrictions are once again being eased in many countries, including the UK. However, travellers need to be aware that COVID-19 remains a worldwide risk. Practice nurses have a role to play in supporting UK travellers to make an informed choice about travelling abroad during this ongoing pandemic.
Study on the Articulated Finger Based on Pneumatic Soft Joint
Authors: Shi Kai , Zheng Huayi , Li Jun , Bao Gang
Published: June 2021

This article described a novel pneumatic soft joint used to make articulated soft fingers. This soft joint was designed by improving the basic structure of the fast pneumatic network. The joint was made of high modulus E630 silicon, which can increase the reverse exhaust speed through its high structural elasticity. Aramid fabric was used to restrain the non-working direction of joints to reduce ineffective expansion, thereby reducing air consumption. The kinematics and statics model of the joint was established by the piecewise constant curvature (PCC) method, and the model was proved to be effective. The silicone staging pouring process was used in the manufacture of joints and fingers, which can achieve high-quality product rates. A soft finger actuator composed of three soft joints was designed and manufactured, whose length was 1.3 times the human finger. The finger can nimbly achieve the target motion, and the gripping force of the fingertip can reach 7.1N. The articulated soft finger actuator has applications in soft dextrous hands and soft gripper.
Single-shot ultrasound-modulated optical tomography with enhanced speckle contrast
Authors: Yuan Dean , Luo Jiawei , Wu Daixuan , Zhang Runsen , Lai Puxiang , Li Zhaohui , Shen Yuecheng
Published: June 2021

Ultrasound-modulated optical tomography (UOT) images optical contrast deep inside biological tissue. Among existing approaches, camera-based parallel detection is beneficial in modulation depth but is limited to the relatively slow framerate of cameras. This condition prevents such a scheme from achieving maturity to image live animals with sub-millisecond speckle correlation time. In this work, we developed on-axis single-shot UOT by investigating the statistics of speckles, breaking the restriction imposed by the slow camera framerate. As a proof of concept, we experimentally imaged a one-dimensional absorptive object buried inside a moving scattering medium with speckle correlation time down to 0.48 ms. We envision that this single-shot UOT is promising to cope with live animals with fast speckle decorrelation.
Femtosecond multi-10-mJ pulses at 2 µm wavelength by compression in a hollow-core fiber
Authors: Nagy Tamas , von Grafenstein Lorenz , Ueberschaer Dennis , Griebner Uwe
Published: June 2021

High-energy few-ps pulses from a Ho:YLF chirped pulse amplifier operating at a 1 kHz repetition rate are compressed in a two-stage arrangement to sub-90-fs duration. The energy of the compressed pulses is more than 20 mJ at an average power of 20 W. In the first stage, the duration of the 2.8 ps, 40 mJ pulses at 2.05 µm wavelength was reduced to 1.4 ps by using nonlinear propagation in air. Subsequently, the pulses were further compressed to 86 fs after spectral broadening in a 3-m-long Kr-filled stretched flexible hollow-core fiber. The high photon flux, peak power, and excellent beam quality and stability make this light source highly attractive for fs pulse generation in the extreme ultraviolet (XUV) to x-ray spectral range for time-resolved XUV spectroscopy or measurements of structural dynamics in solids.
Double-pass pre-chirp managed amplification with high gain and high average power
Authors: Zhang Yao , Wang Jingshang , Teng Hao , Fang Shaobo , Wang Junli , Chang Guoqing , Wei Zhiyi
Published: June 2021

We demonstrate, to the best of our knowledge, the first double-pass pre-chirp managed fiber amplifier. The double-pass fiber amplifier exhibits high gain allowing us to amplify chirped picosecond pulses from 20 mW to 113 W in a rod-type Yb-fiber corresponding to 38 dB gain. We study the dependence of static mode degradation (SMD) on the nonlinear phase shift (NPS) accumulated by the amplified pulse. Our results indicate that a larger nonlinear phase shift results in stronger nonlinear polarization evolution of the fundamental mode and leads to a lower threshold for SMD. After optimization, our pre-chirp managed amplifier seeded by 80 mW pulses delivers 102 W amplified power from the main output. The amplified pulses are compressed to 37 (55) fs with 90 (100) W average power by a grating pair (chirped mirrors). The double-pass configuration significantly simplifies the implementation of pre-chirp managed fiber amplifiers leading to an extremely compact system.
Information extraction from polarized MMW radiation based on the weak correlation between emission and reflection
Authors: Hu Yan , Su Jinlong , Hu Fei , Wu Hongfei , Yang Liu
Published: June 2021

Millimeter-wave (MMW) radiometry has been used in a vast and growing assortment of applications. Several MMW discriminators have been proposed and achieved good results in material classification and recognition. However, these discriminators are difficult to measure accurately in the real world. In this article, we defined two discriminators, emissive degree of polarization (EDoP) and reflecting DoP (RDoP), and proposed a physically based method using the characteristic of weak correlation of the emission part and reflection part of MMW radiation as an optimization criterion to obtain the optimal estimation of RDoP. Most measurement errors, such as the thermal noise of the radiometer, radiative transfer, antenna pattern, and calibration error, will not affect our method, and thus it is easy to implement in the real world. The effectiveness of our method has been verified by experiments. Our method only needs to measure the brightness temperature of horizontal polarization and vertical polarization. Based on RDoP, more information such as other discriminators, physical temperature, equivalent permittivity, reflectivity, and surrounding brightness temperature can be retrieved. Potential applications include liquid ingredient analysis, terrain monitoring, and security checks.
Longitudinal effects of gender minority stressors on substance use and related risk and protective factors among gender minority adolescents
Authors: Katz-Wise Sabra L. , Sarda Vishnudas , Austin S. Bryn , Harris Sion Kim
Published: June 2021

Purpose

Gender minority (GM) adolescents, who have a different gender identity than their sex assigned at birth, may use substances as a coping strategy in response to GM-related stressors. This study examined longitudinal effects of gender minority stressors on substance use in GM adolescents, and related risk factors (internalized transphobia, depressive symptoms, anxious symptoms) and protective factors (resilience, gender-related pride, family functioning, social support, gender-related community connectedness).

Methods

Participants were 30 GM adolescents, ages 13–17 years, from the U.S. community-based longitudinal Trans Teen and Family Narratives Project. Participants completed an online survey every 6 months across 2 years (5 waves; data collected 2015–2019).

Results

Exposure to gender minority stressors was associated with higher odds of alcohol use. Across models, internalized transphobia (risk factor), resilience (protective factor), and gender-related pride (protective factor) were the most significant mediators of associations between gender minority stressors and substance use. Family functioning and social support (protective factors) significantly moderated the association between gender minority stressors and alcohol use, such that family functioning and social support were protective for alcohol use at lower levels of gender minority stress, but not at higher levels.

Conclusion

Results suggest that GM adolescents engage in substance use as a coping strategy in response to gender minority stressors. A number of hypothesized risk and protective factors mediated or moderated these associations. Future interventions with GM adolescents should focus efforts on addressing internalized transphobia as a risk factor and strengthening resilience, gender-related pride, and family functioning as protective factors for substance use.
A new Oligocene-Miocene tree from Panama and historical Anacardium migration patterns
Authors: Rodríguez-Reyes Oris , Estrada-Ruiz Emilio , Monje Dussán Camila , de Andrade Brito Lilian , Terrazas Teresa
Published: June 2021

Migration of Boreotropical megathermal taxa during the Oligocene and Miocene played a key role in assembling diversity in tropical regions. Despite scattered fossil reports, the cashew genus Anacardium offers an excellent example of such migration. The fossil woods described here come from localities in Veraguas, Panama mapped as Oligocene-Miocene. We studied, described, and identified two well-preserved specimens using wood anatomical characteristics and completed extensive comparisons between fossil and extant material. The studied fossil woods share several diagnostic features with the modern Anacardium genus, including large solitary vessels, large intervessel-pitting, a simple vessel-ray pitting pattern, and mostly 1–3 seriate rays with large rhomboidal solitary crystals. We propose a new fossil species named Anacardium gassonii sp. nov., that adds an essential piece to the understanding of the historical biogeography of the genus. In addition, our findings confirm previous interpretations of this species’ migration from Europe to North America and its crossing through Panama, leading to subsequent diversification in South America. This discovery provides an important link to the historical migration patterns of the genus, supporting the notion of an Eocene migration to the Neotropics via Boreotropical bridges, as well as an Oligocene-Miocene crossing of Central America followed by diversification in South America.
Severity of non-alcoholic steatohepatitis is not linked to testosterone concentration in patients with type 2 diabetes
Authors: Dayton Kristin Alexandra , Bril Fernando , Barb Diana , Lai Jinping , Kalavalapalli Srilaxmi , Cusi Kenneth
Published: June 2021

Background

Hypogonadism is reported to occur in non-alcoholic fatty liver disease (NAFLD), but earlier studies used low-sensitivity diagnostic techniques (CT, ultrasound), for NAFLD diagnosis. We hypothesized that if hypogonadism was due to NAFLD, and not solely attributable to underlying obesity/diabetes, it would be more severe in the presence of steatohepatitis (NASH). To examine the influence of liver disease on testosterone in males with type 2 diabetes mellitus (T2DM), we used gold-standard liver imaging with MR-spectroscopy (1H-MRS), and performed liver biopsies to grade/stage the NAFLD.

Methods

In this cross-sectional study, we measured in 175 males with T2DM total and free testosterone, markers of insulin resistance, and intrahepatic triglyceride content (IHTG) by1H-MRS. Those with NAFLD on imaging underwent a liver biopsy.

Results

Total testosterone was higher in the group without NAFLD (“No-NAFLD”; n = 48) compared to isolated steatosis (IS; n = 62) or NASH (n = 65) (385 ± 116 vs. 339 ± 143 vs. 335 ± 127 ng/ml, ptrend0.03). Testosterone was also lower in obese vs. non-obese subjects in both the No-NAFLD and IS groups (p = 0.06 and p = 0.11, respectively), but not in obese vs. non-obese patients with NASH (p = 0.81). IHTG was independently associated with total testosterone (ß = -4.8, p = 0.004). None of the liver histology characteristics were associated with lower testosterone.

Conclusions

NAFLD is linked to lower total testosterone in patients with T2DM, but likely given a common soil of insulin resistance/obesity and not from the severity of liver necroinflammation or fibrosis. Nevertheless, clinicians should consider screening patients with T2DM and NAFLD for hypogonadism.
Can we screen for pancreatic cancer? Identifying a sub-population of patients at high risk of subsequent diagnosis using machine learning techniques applied to primary care data
Authors: Malhotra Ananya , Rachet Bernard , Bonaventure Audrey , Pereira Stephen P. , Woods Laura M.
Published: June 2021

Background

Pancreatic cancer (PC) represents a substantial public health burden. Pancreatic cancer patients have very low survival due to the difficulty of identifying cancers early when the tumour is localised to the site of origin and treatable. Recent progress has been made in identifying biomarkers for PC in the blood and urine, but these cannot be used for population-based screening as this would be prohibitively expensive and potentially harmful.

Methods

We conducted a case-control study using prospectively-collected electronic health records from primary care individually-linked to cancer registrations. Our cases were comprised of 1,139 patients, aged 15–99 years, diagnosed with pancreatic cancer between January 1, 2005 and June 30, 2009. Each case was age-, sex- and diagnosis time-matched to four non-pancreatic (cancer patient) controls. Disease and prescription codes for the 24 months prior to diagnosis were used to identify 57 individual symptoms. Using a machine learning approach, we trained a logistic regression model on 75% of the data to predict patients who later developed PC and tested the model’s performance on the remaining 25%.

Results

We were able to identify 41.3% of patients < = 60 years at ‘high risk’ of developing pancreatic cancer up to 20 months prior to diagnosis with 72.5% sensitivity, 59% specificity and, 66% AUC. 43.2% of patients >60 years were similarly identified at 17 months, with 65% sensitivity, 57% specificity and, 61% AUC. We estimate that combining our algorithm with currently available biomarker tests could result in 30 older and 400 younger patients per cancer being identified as ‘potential patients’, and the earlier diagnosis of around 60% of tumours.

Conclusion

After further work this approach could be applied in the primary care setting and has the potential to be used alongside a non-invasive biomarker test to increase earlier diagnosis. This would result in a greater number of patients surviving this devastating disease.
Modelling future trajectories of obesity and body mass index in England
Authors: Cobiac Linda J. , Scarborough Peter
Published: June 2021

Background

Obesity is a leading risk for poor health outcomes in England. We examined best- and worst-case scenarios for the future trajectory of the obesity epidemic.

Methods

Taking the last 27 years of Health Survey for England data, we determined both position and shape of the adult body mass index (BMI) distribution and projected these parameters 20 years forward in time. For the best-case scenario, we fitted linear models, allowing for a quadratic relationship between the outcome variable and time, to reflect a potential reversal in upwards trends. For the worst-case scenario, we fitted non-linear models that applied an exponential function to reflect a potential flattening of trends over time. Best-fitting models were identified using Monte Carlo cross-validation on 1991–2014 data, and predictions of population prevalence across five BMI categories were then validated using 2015–17 data.

Results

Both linear and non-linear models showed a close fit to observed data (mean absolute error <2%). In the best-case scenario, the proportion of the population at increased risk (BMI≥25kg/m2) is predicted to fall from 66% in 2017 to 53% (95% confidence interval: 41% to 64%) in 2035. In the worst-case scenario, this proportion is likely to remain relatively stable overall– 64% (37% to 90%) in 2035 –but with an increasing proportion of the population at highest risk (BMI≥35kg/m2).

Conclusions

While obesity prediction depends on chosen modelling methods, even under optimistic assumptions it is likely that the majority of the English population will still be at increased risk of disease due to their weight until at least 2035, without greater allocation of resources to effective interventions.
A novel method of screening combinations of angiostatics identifies bevacizumab and temsirolimus as synergistic inhibitors of glioma-induced angiogenesis
Authors: Dorrell Michael I. , Kast-Woelbern Heidi R. , Botts Ryan T. , Bravo Stephen A. , Tremblay Jacob R. , Giles Sarah , Wada Jessica F. , Alexander MaryAnn , Garcia Eric , Villegas Gabriel , Booth Caylor B. , Purington Kaitlyn J. , Everett Haylie M. , Siles Erik N. , Wheelock Michael , Silva Jordan A. , Fortin Bridget M. , Lowey Connor A. , Hale Allison L. , Kurz Troy L. , Rusing Jack C. , Goral Dawn M. , Thompson Paul , Johnson Alec M. , Elson Daniel J. , Tadros Roujih , Gillette Charisa E. , Coopwood Carley , Rausch Amy L. , Snowbarger Jeffrey M.
Published: June 2021

Tumor angiogenesis is critical for the growth and progression of cancer. As such, angiostasis is a treatment modality for cancer with potential utility for multiple types of cancer and fewer side effects. However, clinical success of angiostatic monotherapies has been moderate, at best, causing angiostatic treatments to lose their early luster. Previous studies demonstrated compensatory mechanisms that drive tumor vascularization despite the use of angiostatic monotherapies, as well as the potential for combination angiostatic therapies to overcome these compensatory mechanisms. We screened clinically approved angiostatics to identify specific combinations that confer potent inhibition of tumor-induced angiogenesis. We used a novel modification of theex ovochick chorioallantoic membrane (CAM) model that combined confocal and automated analyses to quantify tumor angiogenesis induced by glioblastoma tumor onplants. This model is advantageous due to its low cost and moderate throughput capabilities, while maintaining complexin vivocellular interactions that are difficult to replicatein vitro. After screening multiple combinations, we determined that glioblastoma-induced angiogenesis was significantly reduced using a combination of bevacizumab (Avastin®) and temsirolimus (Torisel®) at doses below those where neither monotherapy demonstrated activity. These preliminary results were verified extensively, with this combination therapy effective even at concentrations further reduced 10-fold with a CI value of 2.42E-5, demonstrating high levels of synergy. Thus, combining bevacizumab and temsirolimus has great potential to increase the efficacy of angiostatic therapy and lower required dosing for improved clinical success and reduced side effects in glioblastoma patients.