Gaps in humanitarian WASH response: perspectives from people affected by crises, practitioners, global responders, and the literature.

Water, sanitation, and hygiene (WASH) interventions prevent and control disease in humanitarian response. To inform future funding and policy priorities, WASH 'gaps' were identified via 220 focus-group discussions with people affected by crises and WASH practitioners, 246 global survey respondents, and 614 documents. After extraction, 2,888 (48 per cent) gaps from direct feedback and 3,151 (52 per cent) from literature were categorised.

Lessons learned from conducting six multi-country mixed-methods effectiveness research studies on water, sanitation, and hygiene (WASH) interventions in humanitarian response.

Background: Provision of safe water, sanitation, and hygiene (WASH) to affected populations in humanitarian emergencies is necessary for dignity and communicable disease control. Additional evidence on WASH interventions is needed in humanitarian settings. Between 2008 and 2019, we completed six multi-country, mixed-methods effectiveness studies in humanitarian response on six different WASH interventions.

Evidence summary of water, sanitation, and hygiene (WASH) coordination in humanitarian response.

Providing water, sanitation, and hygiene (WASH) to emergency-affected populations is necessary for reasons of dignity and disease control. Such a (humanitarian) response is coordinated via the 'cluster approach'. This study utilises a literature review, an appraisal of and analysis of Global WASH Cluster (GWC) documentation, and key informant interviews to summarise the outcomes and impacts of GWC coordination.

Molecular targeting of renal cell carcinoma by an oral combination.

The 5-year survival rate of patients with metastatic renal cell carcinoma (mRCC) is <12% due to treatment failure. Therapeutic strategies that overcome resistance to modestly effective drugs for mRCC, such as sorafenib (SF), could improve outcome in mRCC patients. SF is terminally biotransformed by UDP-glucuronosyltransferase-1A9 (A9) mediated glucuronidation, which inactivates SF.

A Novel Splice Variant of HYAL-4 Drives Malignant Transformation and Predicts Outcome in Patients with Bladder Cancer.

Purpose: Poor prognosis of patients with muscle-invasive bladder cancer that often metastasizes drives the need for discovery of molecular determinants of bladder cancer progression. Chondroitin sulfate proteoglycans, including CD44, regulate cancer progression; however, the identity of a chondroitinase (Chase) that cleaves chondroitin sulfate from proteoglycans is unknown. HYAL-4 is an understudied gene suspected to encode a Chase, with no known biological function.

RB constrains lineage fidelity and multiple stages of tumour progression and metastasis.

Mutations in the retinoblastoma (RB) tumour suppressor pathway are a hallmark of cancer and a prevalent feature of lung adenocarcinoma. Although RB was the first tumour suppressor to be identified, the molecular and cellular basis that underlies selection for persistent RB loss in cancer remains unclear. Methods that reactivate the RB pathway using inhibitors of cyclin-dependent kinases CDK4 and CDK6 are effective in some cancer types and are currently under evaluation for the treatment of lung adenocarcinoma.

Household Water Treatment and Cholera Control.

Water, sanitation, and hygiene are one part of a cholera control strategy. Household water treatment (HWT) in particular has been shown to improve the microbiological quality of stored water and reduce the disease burden. We conducted a systematic review of published and gray literature to determine the outcomes and impacts of HWT in preventing cholera specifically.

A Systematic Review and Meta-Analysis of the Association between Water, Sanitation, and Hygiene Exposures and Cholera in Case-Control Studies.

Case-control studies are conducted to identify cholera transmission routes. Water, sanitation, and hygiene (WASH) exposures can facilitate cholera transmission (risk factors) or interrupt transmission (protective factors). To our knowledge, the association between WASH exposures and cholera from case-control studies has not been systematically analyzed.

Molecular Characterization of Renal Cell Carcinoma: A Potential Three-MicroRNA Prognostic Signature.

Aberrantly expressed miRNAs promote renal cell carcinoma (RCC) growth and metastasis and are potentially useful biomarkers for metastatic disease. However, a consensus clinically significant miRNA signature has not been identified. To identify an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach.

Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.

Background: Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets.

Methods: Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase.

Systematic Inactivation of Chromatin-Regulating Enzymes Identifies Setd2 as a Potent Tumor Suppressor in Lung Adenocarcinoma.

Chromatin-modifying genes are frequently mutated in human lung adenocarcinoma, but the functional impact of these mutations on disease initiation and progression is not well understood. Using a CRISPR-based approach, we systematically inactivated three of the most commonly mutated chromatin regulatory genes in two Kras-driven mouse models of lung adenocarcinoma to characterize the impact of their loss. Targeted inactivation of SWI/SNF nucleosome-remodeling complex members () or had complex effects on lung adenocarcinoma initiation and progression.

Antitumor activity of sulfated hyaluronic acid fragments in pre-clinical models of bladder cancer.

Tumor cell-derived hyaluronidase HYAL-1 degrades hyaluronic acid (HA) into angiogenic fragments (AGF: 10-12 disaccharides). AGF support tumor growth and progression. Urine and tissue HAase/HYAL-1 levels are sensitive markers for high-grade bladder cancer (BCa) and its metastasis.

Recombinase-based conditional and reversible gene regulation via XTR alleles.

Synthetic biological tools that enable precise regulation of gene function within in vivo systems have enormous potential to discern gene function in diverse physiological settings. Here we report the development and characterization of a synthetic gene switch that, when targeted in the mouse germline, enables conditional inactivation, reports gene expression and allows inducible restoration of the targeted gene. Gene inactivation and reporter expression is achieved through Cre-mediated stable inversion of an integrated gene-trap reporter, whereas inducible gene restoration is afforded by Flp-dependent deletion of the inverted gene trap.

Dietary supplement 4-methylumbelliferone: an effective chemopreventive and therapeutic agent for prostate cancer.

Background: Prevention and treatment of advanced prostate cancer (PCa) by a nontoxic agent can improve outcome, while maintaining quality of life. 4-methylumbelliferone (4-MU) is a dietary supplement that inhibits hyaluronic acid (HA) synthesis. We evaluated the chemopreventive and therapeutic efficacy and mechanism of action of 4-MU.

The impact of water, sanitation, and hygiene interventions on the health and well-being of people living with HIV: a systematic review.

Background: Access to improved water supply and sanitation is poor in low-income and middle-income countries. Persons living with HIV/AIDS (PLHIV) experience more severe diarrhea, hospitalizations, and deaths from diarrhea because of waterborne pathogens than immunocompetent populations, even when on antiretroviral therapy (ART).

Methods: We examined the existing literature on the impact of water, sanitation, and hygiene (WASH) interventions on PLHIV for these outcomes: (1) mortality, (2) morbidity, (3) retention in HIV care, (4) quality of life, and (5) prevention of ongoing HIV transmission.

Effectiveness of chlorine dispensers in emergencies: case study results from Haiti, Sierra Leone, Democratic Republic of Congo, and Senegal.

Dispensers are a source-based water quality intervention with promising uptake results in development contexts. Dispenser programs include a tank of chlorine with a dosing valve that is installed next to a water source, a local Promoter who conducts community education and refills the Dispenser, and chlorine refills. In collaboration with response organizations, we assessed the effectiveness of Dispensers in four emergency situations.

Enantioselective pharmacokinetics of primaquine in healthy human volunteers.

Primaquine (PQ), a racemic drug, is the only treatment available for radical cure of relapsing Plasmodium vivax malaria and blocking transmission of P. falciparum malaria. Recent studies have shown differential pharmacologic and toxicologic profiles of individual PQ enantiomers in rodent, dog, and primate animal models.

Differential expression of SDF-1 isoforms in bladder cancer.

Purpose: SDF-1 is a ligand of the chemokine receptors CXCR4 and 7. The 6 known SDF-1 isoforms are generated by alternative mRNA splicing. While SDF-1 expression has been detected in various malignancies, only few groups have reported differential expression of SDF-1 isoforms and its clinical significance.

Dietary supplement hymecromone and sorafenib: a novel combination for the control of renal cell carcinoma.

Purpose: Current treatments for metastatic renal cell carcinoma do not extend survival beyond a few months. Sorafenib is a targeted drug approved for metastatic renal cell carcinoma but it has modest efficacy. Hymecromone is a nontoxic dietary supplement with some antitumor activity at high doses of 450 to 3,000 mg per day.

C-X-C chemokine receptor 7: a functionally associated molecular marker for bladder cancer.

Background: C-X-C chemokine receptor 4 (CXCR4) and CXCR7 are 7-transmembrane chemokine receptors of the stroma-derived factor (SDF-1). CXCR4, but not CXCR7, has been examined in bladder cancer (BCa). This study examined the functional and clinical significance of CXCR7 in BCa.

Chemokine and chemokine receptor expression in kidney tumors: molecular profiling of histological subtypes and association with metastasis.

Purpose: Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms.

Molecular characterization of kidney cancer: association of hyaluronic acid family with histological subtypes and metastasis.

Background: Molecular profiling of renal cell carcinomas (RCCs) may improve the distinction between oncocytoma and malignant RCC subtypes and aid in early detection of metastasis. The hyaluronic acid (HA) family includes HA synthases (HAS1, HAS2, HAS3), hyaluronidases (HYAL-1, HYAL-2, HYAL-3, HYAL-4, PH20, HYAL-P1), and HA receptors (CD44s, CD44v, RHAMM). HA family members promote tumor growth and metastasis.

Targeting hyaluronidase for cancer therapy: antitumor activity of sulfated hyaluronic acid in prostate cancer cells.

The tumor cell-derived hyaluronidase (HAase) HYAL-1 degrades hyaluronic acid (HA) into proangiogenic fragments that support tumor progression. Although HYAL-1 is a critical determinant of tumor progression and a marker for cancer diagnosis and metastasis prediction, it has not been evaluated as a target for cancer therapy. Similarly, sulfated hyaluronic acid (sHA) has not been evaluated for biological activity, although it is an HAase inhibitor.